Isometric Contraction and Relaxation Times of Right and. Left Ventricles in Normal Subjects and in Patients

Transcription

1 Isometric Contraction and Relaxation Times of Right and Left Ventricles in Normal Subjects and in Patients with Right Ventricular Overloading Measured with Bidirectional Echocardiography Morio ITO, M.D., Takehiko FUJINO, M.D., Emiko KURATA, M.D., Shozo KANAYA, M.D., Masanori FUJINO, M.D., Sunao IMANISHI, M.D., Hideo YASUDA, M.D., and Teruki UENO, M.D. SUMMARY With the use of bidirectional echocardiography, the isometric contraction (ICT) and relaxation times (IRT) of both ventricles were measured in 14 normal subjects (N), 6 cases with right ventricular (RV) diastolic overloading (DO), and 5 cases with RV systolic overloading (SO). The RVDO group consisted of patients with atrial septal defect of ostium secundum type who had large left-to-right shunting, and the RVSO group those with pulmonary hypertension of various origins. The mean ICT and IRT in N were 28.5 }4.8 and 43.8 }1.7msec for RV, and 43.3 }5.6 and 60.9 }9.0msec for left ventricle (LV), respectively. The RVDO group showed no significant change in the mean ICT and IRT of RV (29.7 }4.6 and 54.3 }11.8msec, respectively), but significantly greater means of ICT and IRT of LV (58.5 }9.5 and 83.6 }14.1msec, respectively). In the RVSO group, the mean ICT and IRT were 51.0 }4.1 and 86.8 }8.2msec for RV, and 72.4 }12.2 and }20.4msec for LV, respectively. These values were all significantly greater than the means for both N and RVDO groups, except that the mean ICT of LV was insignificantly different between the RVDO and RVSO groups. It was noted that the intervals of LV tended to increase with the increasing intervals of RV, suggesting the changes in LV function secondarily due to RV overloading. It was concluded that the measurement of ICT and IRT of both ventricles is of clinical value for evaluation of overall cardiac function in the patients with RV overloading. Additional Indexing Words: Atrial septal defect Pulmonary hypertension Left ventricular function Preload Afterload Contractility Compliance From the First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka 812, Japan. Received for publication July 25,

2 194 ITO, ET AL. Jap. Heart J. March, 1978 HE left ventricular (LV) isometric contraction (ICT) and relaxation times (IRT) have been measured by various non-invasive techniques, and the clinical values of these intervals in the evaluation of LV function have been well recognized. 1)-7) However, to our best knowledge, no report have been published on the non-invasive measurement of the ICT and IRT of right ventricle (RV). The non-invasive estimation of these intervals, if possible, would offer sensitive indicators of the state of RV function. In addition, the previous studies indicated that the functional changes in cardiac chamber of one side could influence the behavior of the contralateral side, suggesting the importance of measurement of the time intervals of both ventricles for evaluation of overall cardiac function.8)-14) Recently, we developed a new echocardiographic method, named "bidirectional echocardiography", by which the echoes of any 2 directions could be simultaneously recorded.15),16) This method enabled us to record simultaneously the semilunal and atrioventricular valves and hence to measure the ICT and IRT of either ventricle. The present paper is concerned with the ICT and IRT of both ventricles measured with this method in normal subjects and in patients with RV overloading, studying: 1) how these intervals of RV are affected by the RV diastolic (DO) and systolic overloading (SO), and 2) how the RV overloading alters the LV function as measured by ICT and IRT. MATERIALS AND METHODS Fourteen healthy subjects (12 males and 2 females) and 11 patients with RV Table I. Age, R-R interval, Isometric Contraction and Relaxation Abbreviations: RV and LV: right and left ventricles, ICT and IRT: isometric contraction and relaxation times, RAMP: right atrial mean pressure, RVSP and PASP: right ventricular and pulmonary artery systolic pressures, Qp/Qs: pulmonary-to-systemic flow ratio, H: healthy

3 Vol.19 No.2 ISOMETRIC CONTRACTION AND RELAXATION TIMES 195 overloading (6 males and 5 females) were studied. Their ages are shown in Table I. The selection of subjects was based on the clearly demonstrated cusp echoes, in which at least the ICT and IRT of RV could be measured. All patients with RV overloading have undergone the clinical examinations including electrocardiography, vectorcardiography, phonocardiography, chest roentgenography, echocardiography, and right heart catheterization. On the basis of these clinical observations, the patients were divided into 2 groups: RVDO and RVSO groups. The former consisted of 6 cases with atrial defect septal of ostium secundum type (ASD) who had large left-to-right shunting. These patients had the pulmonary-tosystemic flow ratio of 3.2 to 5.9 (mean: 4.22 }1.02) and pulmonary artery (PA) systolic pressure of 22 to 56mmHg (mean: 32.7 }12.1mmHg). The latter group included 5 cases with pulmonary hypertension (PH) of various origins. The diagnosis of these patients were ASD with PH in 3 cases, ventricular septal defect with PH in 1 and primary PH in 1. The PA systolic pressure and pulmonary-tosystemic flow ratio in these cases ranged 79 to 98mmHg (mean: 90.6 }10.4mmHg) and 0.51 to 1.8 (mean: 1.13 }0.55), respectively. All patients in both groups were normotensive and had no rheumatic heart disease. The subjects served as healthy control were considered to have no cardiac abnormality by the clinical examinations including history, physical examinations, blood pressure, electrocardiography, phonocardiography, and echocardiography. Their ages were 14 to 28 years (mean: 19.3 }5.3 years), being signifi cantly less than the mean ages of the patients with RVDO and RVSO (43.5 }9.5 and 40.6 }11.7 years, respectively) (Table I). However, the R-R intervals showed no significant difference between different groups. The equipment and recording method of bidirectional echocardiography were the same as described previously.15),16) The bidirectional echocardiograms were recorded on strip chart with the paper speed of 100mm/sec simultaneously with the lead II electrocardiogram. The aortic (AV) and mitral valve (MV) echoes, or the pulmonic (PV) and tricuspid valve (TV) echoes were simultaneously recorded. Times, and Catheterization Data in the Subjects Studied control, DO and SO: diastolic and systolic overload, ns, *, **, ***, and ****: p>0.05, 0.05 >p>0.01, 0.01>p>0.005, 0.005>p>0.001, and 0.001>p.

4 196 ITO, ET AL. Jap. HeartJ. M arch, 1978 Fig.1. Bidirectional echocardiograms of mitral (MV) and aortic valves (AV) recorded from a normal subject (panel A) and a patient with primary pulmonary hypertension (panel B). Note the marked prolongation of both the ICT and IRT of LV in panel B compared with the intervals in panel A. Other abbreviations are the same as in Table I. See text for further explanations. Calibrations are 40mm and 200msec. The ICT and IRT of LV were respectively measured from the closure of MV to the opening of AV and from the closure of AV to the opening of MV (Fig.1), and the ICT and IRT of RV from the closure of TV to the opening of PV and from the closure of PV to the opening of TV (Fig.2). According to Rubenstein et al,6) the opening and closing points of atrioventricular valves were respectively defined as the onset of the most rapid anterior motion of anterior leaflet echo in the early diastole (D') and the ternimation of the last rapid posterior motion of anterior leaflet echo in the end-diastole (Co). RESULTS The ICT and IRT of both ventricles in all subjects are shown in Table I and Fig.3, and the illustrative cases are demonstrated in Figs.1 and 2.

5 Vol.19 No.2 ISOMETRIC CONTRACTION AND RELAXATION TIMES 197 Fig.2. Bidirectional echocardiograms of tricuspid (TV) and pulmonic valves (PV) recorded from a normal subject (panel A) and a patient with Eisenmenger complex (atrial septal defect with pulmonary hypertension) (panel B). Note the prolongation of both the ICT and IRT of RV in panel B compared with the intervals in panel A. Other abbreviations are the same as in Table I. See text for further explanations. Calibrations are 40mm and 200msec. The mean ICT and IRT of RV in the normal subjects were 28.5 }4.8 and 43.8 }1.7msec, respectively, and those of LV 43.3 }5.6 and 60.9 }9.0msec, respectively. Compared with the normal values, the RVDO group showed slight, but insignificant increases in the mean ICT and IRT of RV (29.7 } 4.6 and 54.3 }11.8msec, respectively), and significantly greater mean values of LV (58.0 }9.5 and 83.6 }14.1msec, respectively). In the RVSO group, the mean ICT and IRT of RV were 51.0 }4.1 and 86.8 }8.2msec, respectively, and those of LV 72.4 }12.2 and }20.4msec, respectively. These values for the RVSO group were all significantly greater than the mean values for both the healthy and RVDO groups, except that the mean ICT of LV showed no significant difference compared with RVDO (Table I).

6 198 ITO, ET AL. Jap. HeartJ. M arch, 1978 Fig.3. Comparison of ICT and IRT of both ventricles in the normal subjects (N), and the patients with RVDO and RVSO. Horizontal and vertical bars represent the means and standard deviations, respectively. Other abbreviations are the same as in Table I. See text for further explanations. Fig.4. Correlation of ICT and IRT of ipsilateral ventricle., ž, : healthy, RVDO, and RVSO. Abbreviations are the same as in Table I. Note the increasing tendency of IRT with the increasing ICT in either ventricle. See text for further explanations. In Fig.4 are shown the correlations between the ICT and IRT. The IRT of either ventricle tended to increase with the increasing ICT of ipsilateral ventricle. As noted in Fig.4, the IRT of either ventricle consistently exceeded the ICT of ipsilateral side. In Fig.5, the relations of intervals of one ventricle

7 Vol.19 No.2 ISOMETRIC CONTRACTION AND RELAXATION TIMES 199 Fig.5. Correlation of the time intervals of one ventricle to the intervals of the contralateral ventricle. Note the increasing tendency of intervals of LV with the increasing intervals of RV. Abbreviations and symbols are the same as in Table I and Fig.4, respectively. See text for further explanations. to those of contralateral side are demonstrated. Both ICT and IRT of LV were consistently greater than those of RV, and the interval of one ventricle tended to increase as the interval of contralateral side increased. DISCUSSION The echocardiography is a sensitive, non-invasive method of delineating coaptation and opening of cardiac valves.18) The bidirectional echocardiography has provided a method to record simultaneously the atrioventricular and semilunal valve echoes, and hence enabled us to determine precisely the ICT and IRT of either ventricle.16) The ICT and IRT of LV have been measured by various, non-invasive methods. Our mean values for the healthy subjects corresponded closely to the means reported by Benchimol et al,19) Nimura et al,1) Weissler et al,5) and Umeda et al7) for the ICT, and to those reported by Nimura et al1) and Spodick et al2) for the IRT. Recently, several authors reported on the non-invasive measurements of pre-ejection period and ejection period of RV with the use of ultrasonic Doppler method,20) electrokymography,21) indirect PA pulse recording,22) and echocardiography.17) Although the ICT and IRT of RV have been measured in normal subjects with cardiac catheterization method,23)-25) no report has been published on the non-invasive measurement. In the present study, the mean values of ICT and IRT of RV were

8 200 ITO, ET AL. Jap. HeartJ. M arch, 1978 insignificantly different between the normal and RVDO groups, and significantly greater in the RVSO group than in the normal and RVDO groups. Although the effects of acute and chronic intervensions on these intervals of RV have received little attention and the elucidation of the mechanisms responsible for the present results requires further studies, the previous studies seem to suggest some possible explanations. The principal determinants of ICT of LV have been described as 1) preload or LV end-diastolic volume, 2) afterload or diastolic aortic pressure, and 3) inotropic state of LV myocardium.26)-29) On the other hand, the IRT of LV has been considered to depend on 1) the level of aortic dicrotic notch pressure, 2) left atrial pressure, and 3) downslope of LV pressure, 1),30) the last factor further depending on the preload, contractility, and compliance of LV.31) The ICT and IRT of RV might be determined by the corresponding factors in the right-sided heart. In the RVSO group studied here, the PA pressure was markedly elevated with the normal or only slightly elevated right atrial pressure. In this group, the hypertrophy of RV myocardioum due to elevated RV pressure would result in the impairment of both contractility and compliance of RV. In dog experiments, the RV hypertrophy induced by PA banding resulted in the decreased contractility and the diminished norepinephrine content of RV papillary muscle,32) and the decreased RV compliance.33) In addition, the reduced preload has been reported in patients with PH.34) The factors such as the increased preload, impairment in both contractility and compliance, and reduced preload would act themselves to prolong either or both of the ICT and IRT of RV, and when operating together there would be a marked prolongation of these intervals, as noted in the present study. In the RVDO group studied here, there existed a marked increase in the RV preload due to large left-to-right shunting at atrial level with slightly elevated pressures of RV and PA. The previous studies have shown that the ICT and IRT of LV can remain unchanged or even tend to be shortened under the condition of LVDO. In acute experiments, the increase of LV preload with constant aortic pressure resulted in the increases of both the rate of rise and fall of LV pressure, thus inducing the shortening of ICT and IRT of LV.27),30) Also in the clinical studies, Real et al noted that the rate of rise and fall of LV pressure increased in the cases with LVDO and decreased in those with LVSO.35) Nimura et al observed the shortened ICT and normal IRT of LV in aortic regurgitation and the prolongation of both intervals in systemic hypertension.1) Braunwald et al noted that the LV compliance in LVDO increased in the acute phase and then decreased in the chronic phase. 29) Also in the RVDO group studied here, the increased RV preload might act to shorten the ICT and IRT of RV, while the slight elevation of PA pressure

9 Vol.19 No.2 ISOMETRIC CONTRACTION AND RELAXATION TIMES 201 acts to prolong these intervals. When 2 factors are operating together, the inter vals of RV can remain almost unchanged as noted in the present study. The present results showed that the ICT and IRT of LV were prolonged in the patients with RVDO and RVSO and that the degree of prolongation of intervals of LV tended to increase with the increasing intervals of RV. It was suggested that RV overloading induces the impairment of LV function. Several possible mechanisms exist to explain such a phenomenon. The impaired LV contractility has been reported in RV overloading. Kelly et al observed the decreases of systolic pressure, systolic wall stress, dp/dt, contractile element velocity and myocardial concentration of norepinephrine in LV of dog with chronic RV failure.9) Salel et al noted abnormal LV contractility indices in the patients with RV overloading.11) Machida and Rappaport observed the alteration of LV compliance and the decreased LV contractility in dogs with pulmonary embolism.10) The so-called "reversed Bernheim phenomenon" would offer another explanation. The septal bulge to the left due to RVDO is considered to result in altered LV geometry and hence in abnormal contractile function. Taylor et al found the reduced distensibility during RV distension.8) Dog with RV overloading has been observed to have decreased LV compliance.9),10) Stool et al noted in dogs that increasing RV systolic pressure to 60mmHg resulted in a 23% decrease in the distance from the septum to lateral wall as concomitant reduction in LV end-diastolic volume and stroke volume.12) Finally the reduced RV stroke output results in the reduced LV preload and hence induces the alteration of LV function indices.13))14) The authors noted the delay in onset of first heart sound in ASD, and attributed this finding to the impaired LV performance secondarily induced by RVDO.36) The present study revealed that the IRT of either ventricle tended to increase as the ICT of ipsilateral ventricle increased, suggesting that there exist hemodynamic determinants common to both ICT and IRT. The increase of afterload induces the prolongation of both intervals. The rate of fall of LV pressure is one of the principal determinants of IRT1),30) and depends, in turn, on the preload and contractility of LV,31) which are known as the important determinants of ICT of LV.26)-29) The mean ages of RVDO and RVSO groups were significantly greater than the mean age of healthy control. Although such age difference might play some role in inducing the longer intervals of patient groups, the previous results on this problem were controversial. Harrison et al noted the increasing tendency of both the ICT and IRT of LV with the increasing ages.37) However, Arevalo and Sakamoto could not find such an age dependency of IRT of both LV and RV measured with catheterization method.23)

10 202 ITO, ET AL. Jap. HeartJ. M arch, 1978 In conclusion, the bidirectional echocardiography provides a sensitive, reliable, non-invasive method for the measurement of ICT and IRT of both ventricles, and the intervals thus measured are the useful indices for the evaluation of overall cardiac function in patients with RV overloading. REFERENCES 1. Nimura Y, Matsuo H, Mochizuki S, Aoki K, Abe H: Analysis of a cardiac cycle of the left side of the heart in cases of the left ventricular overloading or damage with the ultrasound Doppler method. Am Heart J 75: 49, Spodick DH, Kumar S: Atraumatic measurement of the isometric relaxation period of the left ventricle. Aerospace Med 39: 968, Spodick DH, Sudarsham K: Isovolumic contraction period of the left ventricle. Am Heart J 76: 498, Kumar S, Spodick DH: Study of the mechanical events of the left ventricle by atraumatic techniques. Comparison of methods of measurement and their significance. Am Heart J 80: 401, Weissler AM, Schoenfeld CD: Effect of digitalis on systolic intervals in heart failure. Am Heart J 80: 401, Rubenstein JJ, Pohost GM, Dinsmore RE, Harrison JW: The echocardiographic determination of mitral valve opening and closure. Correlation with hemodynamic studies in man. Circulation 51: 98, Umeda T, Okada R, Furuta S, Machii K, Matsuda K, Yamaguchi T: Measurements of isometric contraction time and isometric relaxation times of left ventricle by simultaneous recording of echocardiogram, phonocardiogram and carotid pulse tracing. Heart 7: 325, 1975 (in Japanese) 8. Taylor RR, Covell JW, Sonnenblick EH, Ross J Jr: Dependence of ventricular distensibility on filling of the opposite ventricle. Am J Physiol 213: 711, Kelly DT, Spotnitz HM, Beiser GD, Pierce JE, Epstein SE: Effects of chronic right ventricular volume and pressure loading on left ventricular performence. Circulation 44: 403, Machida K, Rappaport E: Left ventricular function in experimental pulmonary embolism. Jap Heart J 12: 221, Salel A, Mason DT, Amsterdam EA, Zeus R: Depression of left ventricular contractility in primary right ventricular overload. The "reversed Bernheim phenomenon". Circulation 43, 44 (suppl II): II-220, Stool EW, Mullins CB, Leshin SJ, Mitchell JH: Effect of right ventricular volume change from acute pulmonary hypertension on left ventricular dimension. Clin Res 20: 399, Spodick DH, Khan AH, Quarry VM: Systolic and diastolic time intervals in pulsus alterpans: Significance of altering isovolumic relaxation. Am Heart J 87: 5, Gentzler RD, Hunter AS, Gault JH: Preload dependence of ejection fraction. Am J Cardiol 33: 139, Fujino T, Kanaya S, Kurata E, Ito M, Kushitani M, Nakamura K: Bidirectional echocardiography. Its clinical significance. Jap J Ultrason Med 30: 155, 1975 (in Japanese) 16. Fujino T, Ito M, Kanaya S, Kurata E, Kushitani M, Nakamura K: Bidirectional echocardiography. A new method for detection of cardiac cycle. Proceed Jap Acad 53: 91, Nanda NC, Gramiac R, Robinson TI, Shah PM: Echocardiographic evaluation of pulmonary hypertension. Circulation 50: 575, Feigenbaum H: Echocardiography. Lea and Febiger, Philadelphia, Benchimol A, Ellis JG: A study of the period of isovolumic relaxation in normal subjects

11 Vol.19 No.2 ISOMETRIC CONTRACTION AND RELAXATION TIMES 203 and in patients with heart disease. Am J Cardiol 19: 196, Sakakibara H, Tsuda S, Miyatake K, Hayashi T, Beppu S, Asao M, Matsuo H, Nimura Y: Analysis of cardiac cycles of the right ventricle with the ultrasonic Doppler method. (1) Systolic time intervals of the right ventricle. Cardiovasc Sound Bull 4: 415, 1974 (in Japanese) 21. Muramatsu J, Kakubari Y, Ogawa S: Correlative change between the left and right ventricular systolic time intervals in chronic pressure loading heart. Cardiovasc Sound Bull 3: 483, 1973 (in Japanese) 22. Sakamoto T, Matsushima M, Inoue K, Ito U: Clinical and hemodynamic observation of indirect pulmonary artery pulse tracing. Cardiovasc Sound Bull 3: 127, 1973 (in Japanese) 23. Arevalo F, Sakamoto T: On the duration of the isovolmetric relaxation period (IVRP) in dog and man. Am Heart J 67: 651, Braunwald E, Fishman AP, Cournand A: Time relationship of dynamic events in the cardiac chambers, pulmonary artery and aorta in man. Circulat Res 4: 100, Luisada AA, Cortis B: The dynamic events of the normal heart in man. Acta Cardiol 25: 203, Wallace AG, Mitchell JH, Skinner NS, Sarnoff SJ: Duration of the phases of left ventricular systole. Circulat Res 12: 611, Wallace AG, Skinner NS Jr, Mitchell JH: Hemodynamic determinants of the maximal rate of rise of left ventricular pressure. Am J Physiol 205: 30, Metzger CC, Chough CB, Kroetz FW, Leonard JJ: True isometric contraction time. Its correlation with two external indices of ventricular performance. Am J Cardiol 25: 434, Braunwald E, Ross J Jr, Sonnenblick EH: Mechanisms of Contraction of the Normal and Failing Heart. Little, Brown and Co, 2nd ed, Boston, Weisfeldt ML, Scully HE, Fredriken J, Rubenstein JJ, Pohost GM, Bererholm E, Bello AG, Daggett WM: Hemodynamic determinants of maximum negative dp/dt and periods of diastole. Am J Physiol 227: 613, Cohn PF, Leidtke J, Serur J, Sonnenblick EH, Urshel CW: Maximal rate of pressure fall (peak negative dp/dt) during ventricular relaxation. Cardiovasc Res 6: 263, Spann JF Jr, Buccino RA, Sonnenblick EH, Braunwald E: Contractile state of cardic muscle obtained from cats with experimentally produced ventricular hypertrophy and heart failure. Circulat Res 21: 341, Laks MM, Morady F, Garner D, Swan HJC: Relation of ventricular volume, compliance, and mass in the normal and pulmonary arterial banded canine heart. Cardiovasc Res 6: 187, Walcott G, Burchell HB, Brown A Jr: Primary pulmonary hypertension. Am J Med 49: 70, Real A, Gioffre, PA, Nigrimd A, Motolese M: Maximum rate of pressure decline in the normal, hypertrophied and dilated left ventricle in man. Am J Cardiol 29: 286, Ito M, Fujino T, Ito S, Fukumoto T, Kanaya S, Yasuda H, Tetsuo M, Mashiba H: Prolongation of Q-I interval in atrial septal defect. Jap Heart J 18: 164, Harrison TR, Dixon K, Russell RO Jr, Bidwai PS, Coleman HN: The relation of age to the duration of contraction, ejection, and relaxation of the norami human heart. Am Heart J 67: 189, 1964