INFARCTION WITH SYSTEMIC HYPERTENSION

Transcription

1 Br. J. clin. Pharmac. (1979), 8, 233S-238S LABTALOL INFUSION IN ACUT YOCARDIAL INFARCTION WITH SYSTIC HYPRTNSION P.G. ARX & D.S. RID Regional Cardiothoracic Centre, Freeman Hospital, Freeman Road, Newcastle upon Tyne N7 7DN, UK 1 Fifteen patients with suspected acute myocardial infarction and systemic BP of greater than 16/11 mmhg were treated with an incremental infusion of. 2 Systemic BPs were safely and effectively lowered to less than 13 mmhg systolic or 9 mmhg diastolic in all patients. 3 Heart rate, mean pulmonary artery wedge pressure cardiac index and stroke work index were significantly reduced. 4 The dose of varied from 3 mg-44 mg and was significantly higher (mean 295 mg) in those patients with pre-existing systemic hypertension compared with others (mean 133 mg). 5 No side-effects occurred and all patients survived ito leave hospital. Introduction YOCARDIAL infarction complicated by systemic hypertension has been associated with a higher incidence of left ventricular failure, major arrhythmia and hospital death (Fox et al., 1975; Rosenbaum & Levine, 1941). The improved coronary perfusion resulting from raised systemic BP in this situation probably does not compensate for the increased myocardial oxygen consumption occasioned by elevated afterload, with consequent impairment of myocardial function. High serum catecholamine levels are found in myocardial infarction (Siggers et al., 1971) which makes adrenoceptor blockade an attractive approach to lowering systemic BP. However, ac-adrenoceptor blockade with phentolamine in these circumstances is relatively ineffective in reducing systemic BP in those patients with pre-existing hypertension and, moreover, while satisfactorily lowering left ventricular end diastolic BP, increases heart rate and can worsen myocardial ischaemia (Kelly et al., 1973). p- adrenoceptor blockade on the other hand lowers systemic BP and heart rate, but may elevate left ventricular filling pressure (Peter et al., 1978). The combination of a- and f3-adrenoceptor blockade produced by may combine the benefits of the individual approaches, namely, lowering systemic BP, heart rate and left ventricular filling BP, the major determinants of myocardial oxygen consumption (Braunwald, 1969). The purpose of this study was to determine a suitable infusion regimen for in hypertensive infarction and to observe its haemodynamic effects /79/ $1. ethods Patients were admitted to the study if they had a history and/or 12 lead electrocardiogram (CG) suggestive of acute myocardial infarction, and systemic BPs either greater than 16 mmhg systolic or greater than 11 mmhg diastolic, persisting for 2 h after adequate analgesia. Patients were excluded if they: were over 7 yr of age; had chronic airways disease; had bradycardia of less than 6 beats/min; had X-ray evidence of severe left ventricular failure; or had taken 1 adrenoceptorblocking drugs within the previous 48 hours. All patients gave informed consent, and the studies were carried out in the coronary care unit. Daily 12 lead electrocardiogram and SGOT assays were carried out for at least three consecutive days, and WHO criteria were used for infarct diagnosis (World Health Organization, 1959). The CG was continuously displayed and the heart rate determined from a recording of ten consecutive beats. A 12 lead CG was taken before and on completion of infusion, with the chest lead positions marked by an indelible pen. Systemic BP was measured using a sphygmomanometer cuff. Further haemodynamic measurements were made in seven patients (9-15). A thermistor tipped Swan-Ganz catheter was inserted by way of the brachio-cephalic or an antecubital vein and advanced to a pulmonary artery. If the mean occluded pulmonary arterial BP was the same as pulmonary arterial diastolic BP, the catheter tip was withdrawn to a more central position, and the latter BP used to represent left ventricular end diastolic BP acmillan Journals Ltd 1979

2 234S P.G. ARX & D.S. RID (Bauchard et al., 1971). The catheters permitted simultaneous recording of right atrial pressure. Using Bruch transducers, pulmonary arterial and right atrial pressures were continuously displayed on an S & W oscilloscope. Cardiac output determinations were made using a Cardiovascular Instruments CV 6 cardiac output computer, initially using hand injections of 5% dextrose, but latterly using an OP thermodilution injector and 5% dextrose cooled in iced water. The mean of three injections was used for these determinations. The observations recorded were: heart rate and systemic BP; and in those patients with Swan-Ganz catheters: cardiac output, and pulmonary arterial and right atrial pressures. Two sets of observations were taken 15 min apart before infusion, and subsequently observations were recorded every 3 min during infusion. For the first six patients, this was commenced at 1 mg/h with increments every 3 min of 1 mg/hour. For patients 7-15 an initial rate of 3 mg/h with increments of 3 mg/h every 3 min was used. The infusion was continued for 3 min after the systemic systolic BP fell to less than 13 mmhg or the diastolic to less than 9 minhg. If at any time the systemic BP fell to less than 12 mmhg or 8 mmhg diastolic, the infusion was stopped at once. Calculations ean arterial pressure (AP, mmhg) = systemic diastolic + 1/3 (systemic systolic-systemic diastolic) (Yang et al., 1971). Cardiac index (CI: 1/min 1 m2)= (cardiac output/body surface area). Stroke index (SI; mi 1m2) = (CI/heart rate). Stroke work index (SWI; g- m) = (AP-LVDP) x SI x.136, where LVDP = left ventricular end diastolic BP. Observations before and after were compared using the paired t test. Results Fifteen patients were admitted to the study between 8-22 h after the onset of major symptoms. There were eleven men and four women with a mean age of 54 yr (range yr). Thirteen were found to have had myocardial infarction (nine anterior, four inferior) and two were considered to have unstable angina. Five patients had previously diagnosed systemic hypertension, the SGOT peak in these patients being no different from the others (Table 1). Results and dosage are summarized in Table 2. Observations shown were taken immediately before infusion and at the time of cessation. In all cases a satisfactory fall in systemic BP was obtained, the mean fall in systolic BP being 34% (P <.1) and the diastolic BP 29% (P <.1) (Figure 1). In none of the patients did BP fall below 1 mmhg systolic. All patients were in sinus rhythm before and remained in sinus rhythm throughout infusion and during the remainder of their hospital admission. During infusion, heart rate fell in most patients (mean 15%), the fall being significant (P <.5) (Figure 2). Two patients (4 and 5) experienced sinus bradycardia of 54 and 57 beats/min respectively at the end of infusion. ean CI fell by 15% (P <.5) which was primarily due to the Table 1 Patient details Patient Number ean s.d. Age (yr) Sex F F FF SGOT upper limit of normal 37 IU/I Diagnosis Inferior l Antero-lateral I Antero-lateral l Anterior I Unstable angina Anterior l Unstable angina Antero-lateral l Anterior l Interior l Anterior I Inferior l Anterior I Antero-septal l Antero-lateral I Pre-existing hypertension aximum SGOT

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4 236S P.G. ARX & D.S. RID I. cn 15 - The dose of used ranged from 3 to 44 mg (mean 187 mg). There was a significant (p <.5) difference between the doses required by the previously diagnosed hypertensive patients (mean 295 mg) and the others (mean 133 mg). In nine patients, systemic BP began to increase after discontinuing. This increase occurred after about 9 min, and was successfully reduced by further infusion in four cases, the infusion being continued for up to 12 hours. The 12 lead CG changes were variable. In no patient was further ST segment elevation observed during infusion and in seven there was lowering of the ST segments. Patient 13 experienced a second increase in systemic BP peaking at 2/11 mmhg 6 hours after discontinuing. This was associated with chest pain, an increase in the ST segments and second SGOT peak, suggesting extension of the myocardial infarction. No side-effects occurred and no patient ex i- 5 - c 4-3 x 'a2 c u O 1 Pre Post x ) 'a) c 2 C,, Pre Post Figure 3 Individual Cl and SI responses to infusion. ean Cl fall 2.6 to 2.2 I/min/m2 (P <.5). ean SI fall 32 to 3 ml/m2 (NS). 5L Pre Post Figure 1 Individual systolic and diastolic BP responses to infusion. ean systolic fall 184 to 122 mmhg (P<.1). ean diastolic fall 118 to 84 mmhg (P<.1)., Systemic BP; *, diastolic BP. ). 1 5 en a). ) I 13 r o 1 9o 81-7 F 61 5 L Pre Post Figure 2 Individual heart rate response to infusion. ean fall 85 to 72 beats/min (P<.5). fall in heart rate rather than the fall in SI (mean 6%) (Figure 3). Labetalol infusion resulted in a significant fall in LVDP (p <.1). In the five patients in whom it was elevated on admission to the study there was a marked fall, whereas in the remaining two patients with initially normal end diastolic BPs little change occurred (Figure 4). The mean fall of 36% (p <.1) in the SWI largely reflected the fall in the mean arterial pressure. 4-e 2 us ean pulmonary artery wedge pressure (mmhg) Figure 4 Individual mean pulmonary arterial wedge or pulmonary artery diastolic pressure (PAW/PAD) and SWI responses to. ean PAW/PAD fall 17.1 to 11.1 mmhg (P<.1). ean SWI fall 59 to 37 g/m (P<.1).

5 ACUT YOCARDIAL INFARCTION 237S perienced chest pain during infusion. All 15 patients survived and were discharged from hospital. Discussion The advantages of treating myocardial infarction with systemic hypertension, a situation associated with high serum catecholamine levels, by adrenoceptor blockade, were not apparent in a previously described (Kelly et al., 1973) intervention using phentolamine-mediated oa-adrenoceptor blockade. In their study of 11 patients with mean systemic BP greater than 11 mmhg, BP reduction was variable with less satisfactory results in patients with preexisting hypertension. Reduction in LVDP was good (mean 19.9 mmhg), but reflex tachycardia occurred and in two patients recurrence of chest pain necessitated withdrawal of the drug. The use of,badrenoceptor blockade with propranolol has been advocated, and reduction in heart rate and systemic BP have been satisfactory. However, LVDP has been adversely affected, requiring diuretic therapy and even subsequent aortic balloon counterpulsation (Peter et al., 1978). Similarly, problems have been encountered with other pharmacological agents. Nitroprusside infusion (Chiariello et al., 1976) in hypertensive acute infarction lowered systemic BP, but heart rate increased and further ST elevation occurred. A further study (O'Brien et al., 1975) using diazoxide in 2 infarct patients with systemic BPs greater than 18/11 mmhg resulted in increased ST elevation and chest pain in several. On the other hand, it has been shown in a study in 14 patients with systemic BPs of greater than 14/9 mmhg and acute myocardial infarction, BP reduction by trimethaphen resulted in a reduction of infarct size, as predicted from serum creatine kinase (CK) estimations (Shell & Sobel, 1974). However, it has been suggested that the observed CK release would have been lowered by the reduction in coronary filling pressure alone, and therefore does not necessarily reflect myocradial preservation. Furthermore, the timing of the intervention, a minimum of 7 h after hospital admission, would render infarction reduction less probable (aroko et al., 1978). No patients in our study demonstrated further ST elevation during infusion. In several the ST segments fell. However, as this happened over periods of up to 6 h, inference is difficult in view of the natural history of ST changes in acute infarction. In our series, reduced the main determinants of myocardial oxygen consumption, namely heart rate, left ventricular filling pressure and systemic BP. Although this intervention may have occurred at a stage at which reduction of infarct size may no longer have been possible, myocardial performance should have been enhanced and this may account for the lower morbidity and absent mortality compared with previously studied hypertensive acute infarct patients (Fox et al., 1975; Rosenbaum & Levine, 1941). The optimum level to which systemic BP should be reduced in myocardial infarction is not known, and similarly neither is the optimum LVDP. It may be that these parameters should be considered together rather than in isolation in the management of these patients. We view our work as a pilot study. This has shown that incremental infusion is a safe, practical and effective method of lowering systemic BP in myocardial infarction. A further randomized study will be required to establish the validity of the lower morbidity and mortality (absent) in our small group of patients compared with the studies of the natural history of acute myocardial infarction complicated by systemic hypertension. We thank the physicians, nurses and technical staff of the Freeman Hospital Coronary Care Unit for their invaluable assistance, and iss Tina Farrance for secretarial assistance. References BOUCHARD, R.J., GWILT, J.H. & ROSS, J., Jr. (1971). valuation of pulmonary arterial end diastolic pressure as an estimate of left ventricular diastolic pressure in patients with normal and abnormal left ventricular performance. Circulation, 44, BRAUNWALD,. (1969). The determinants of myocardial oxygen consumption. Physiologist, 12, CHIARILLO,., GOLD, H.K., LINBACK, R.C., DAVIS,.A. & AROKO, P.R. (1976). Comparison between the effects of nitroprusside and nitroglycerin on ischaemic injury during acute myocardial infarction. Circulation, 54, FOX, K.., TOLINSON, I.W., PORTAL, R.W. & ABR, C.P. (1975). Prognostic significance of acute systolic hypertension after myocardial infarction. Br. med. J., 3, KLLY, D.T., DLGADO, C.., TAYLOR, D.R., PITT, B. & ROSS, R.S. (1973). Use of phentolamine in acute myocardial infarction associated with hypertension and left ventricular failure. Circulation, 47, AROKO, P.R., KLONR, R.A., YASUDA, T.,,-RBIRO, L.G.T., ACLAN, D. & BRAUNWALD,. (1978). Recent investigations on attempts to limit infarct size. Proc. Astra Conf. "Acute and long term medical managementof myocardial ischaemia". Pp Sweeden: Astra Pharmaceuticals AB.

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