Effects of verapamil on infarct size following experimental coronary occlusion

Smith, H.; Singh, Bramah N.; Nisbet, Heather D.; Norris, R. M.

doi:10.1093/cvr/9.4.569

Cited by 126 publications

(17 citation statements)

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“…Indeed, the order of potency in protecting against ischaemiainduced arrhythmias (verapamil > flunarizine > cinnarizine) is similar to that for inhibition of the slow channel as assessed by their vascular smooth muscle relaxing properties (Tobia, A.J., personal communication). However, the precise mechanism of action of these calcium antagonists, whether it be suppression of slow response action potentials in the myocardium (Dersham & Han, 1981), improvement of conduction (Elharrar et al, 1977), increase in myocardial blood flow (Henry et al, 1978) or a reduction in the degree of ischaemic damage (Smith et al, 1975) cannot be elucidated from these experiments. Moreover, all of these drugs have other pharmacological actions which may contribute to their protective effects during ischaemia.…”

Section: Resultsmentioning

confidence: 99%

The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion‐induced arrhythmias in anaesthetized rats

Fagbemi

Kane

McDonald

et al. 1984

British J Pharmacology

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In male rats, anaesthetized with pentobarbitone, ligation of the main left coronary artery causes an early phase of ventricular arrhythmias which last about 30 min. In approximately 60% of control animals, ventricular fibrillation occurs but since spontaneous reversion to sinus rhythm may occur, mortality is of the order of 30%. When administered intravenously 15 min prior to ligation, verapamil (0.01 and 0.05 mg kg−1), prenylamine (0.5 mg kg−1), flunarizine (0.1, 0.25, 0.5 and 1.0 mg kg−1) and cinnarizine (0.25, 0.5 and 1.0 mg kg−1) protected against these arrhythmias. Higher doses of verapamil (0.1 and 0.5 mg kg−1), prenylamine (5 mg kg−1) and flunarizine (2.5 mg kg−1) did not afford a similar protection and mortality was increased to or above control values. Death was due in prenylamine‐treated rats to atrioventricular block leading to asystole whereas in those administered verapamil or flunarizine it was a consequence of persistent ventricular fibrillation. Prior to ligation, a sustained fall in mean arterial blood pressure was observed only following the administration of the highest doses of prenylamine, flunarizine and cinnarizine. Heart rate was reduced by administration of only the highest dose of prenylamine. These studies show that although the four calcium antagonists studied, i.e. verapamil, prenylamine, flunarizine and cinnarizine do suppress ischaemia‐induced arrhythmias, this protective effect may be limited to a narrow concentration range.

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Section: Resultsmentioning

confidence: 99%

The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion‐induced arrhythmias in anaesthetized rats

Fagbemi

Kane

McDonald

et al. 1984

British J Pharmacology

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“…The decrease in heart rate is beneficial to the ischaemic myocardium as it reduces myocardial oxygen demands (Smith et al, 1975). CPU-23, at the dose exerting antiarrhythmic activity, induced transient hypotension, which is also beneficial to the heart as the afterload is reduced.…”

Section: Discussionmentioning

confidence: 99%

Calcium antagonistic and antiarrhythmic actions of CPU‐23, a substituted tetrahydroisoquinoline

Dong

Sheng

Lee

et al. 1993

British J Pharmacology

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1 The effects of (1-{1-[(6-methoxyl)-naphth-2-yl]}-propyl-2-(1-piperidine)-acetyl-6,7-dimethyoxy-1,2,3,4-tetra-hydroisoquinoline) were studied on mechanical and electrical activities, and intracellular free calcium ([Ca2+]i) of isolated cardiac tissues in order to investigate its spectrum and mechanisms of action in the heart. Its antiarrhythmic and haemodynamic effects in pentobarbitone-anaesthetized rats subjected to coronary artery ligation were also evaluated. 2 CPU-23 at 10-6 10-4 M markedly inhibited slow action potential characteristics in guinea-pig papillary muscles and pace-maker action potential of rabbit sinoatrial node. It affected fast action potential only at 10-4 M. None of the effects of CPU-23 was reversed by washout for up to 2 h.3 Like nifedipine and diltiazem, CPU-23 decreased the heart rate of the isolated perfused heart of the rat. However, in contrast to these two classical calcium antagonists which dose-dependently inhibited the force of contraction, CPU-23 inhibited and stimulated the force of contraction at 10-7-3 x 10-6 M and 10-5 M, respectively. 4 CPU-23 at 10-6 10-5 M inhibited the KCl-induced [Ca2+], increase in the Ca2" medium, but did not affect the caffeine-induced [Ca21], increase in the Ca2'-free medium in isolated ventricular myocytes. 5 CPU-23 at 1-5 mg kg-' reduced dose-dependently ventricular arrhythmias including ventricular ectopic beats, VT and VF as well as mortality during coronary artery ligation. At 2.5-5 mg kg-' it even abolished VF, which was accompanied by 100% survival. 6 It is suggested that CPU-23 has calcium antagonistic properties in cardiac tissues. It selectively blocks the transmembrane influx of extracellular Ca2" through Ca2" channels, thus reducing the heart rate and developed tension, altering the slow action potential characteristics and producing antiarrhythmic effect against ischaemic arrhythmias.

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“…In the second dog, the initial heart rate was 194 beats/min: atrial pacing at 180 beats/min was initiated after 0.3 mg/kg of verapamil but third degree atrioventricular block occurred after 0.6 mg/kg so that ventricular pacing was required. In this case, the pacemaker was switched off for [3][4] beats during recordings since the altered contraction pattern made interpretation of drug-induced changes difficult.…”

Section: Effect Of High-dose Verapamil On Normal Myocardiummentioning

confidence: 99%

Regional contractility. Selective depression of ischemic myocardium by verapamil.

Smith¹,

Goldstein²,

Griffith³

et al. 1976

Circulation

119

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SUMMARY The effects of verapamil (0.02-0.2 mg/kg) on contractility in normal and partially ischemic myocardium were compared with the changes following propranolol (0.01-1.0 mg/kg). Regional contractile function was studied in open-chest dogs with ultrasonic crystals and ischemia was controlled by graded occlusion of a carotid-to-coronary artery shunt. Reduction in shunt perfusion pressure (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) resulted in hypokinesia. Verapamil depressed contractility in ischemic myocardium in 5/5 dogs, but did not alter the maximum velocity of shortening (max V) or end-VERAPAMIL HAS BEEN USED as an antianginal agent in man' and has been shown to prolong survival2 and reduce ST-segment elevation in dogs following acute coronary artery occlusion.3 Its salutary effects on ST segments during acute coronary occlusion occur without associated changes in collateral blood flow or the rate of anaerobic metabolism, suggesting that the drug may reduce ischemic injury by a direct myocardial effect.4Since verapamill and ischemial both interfere with the movement of calcium ions at the cell membrane level, it seemed possible that verapamil might be capable of selectively depressing contractile function in ischemic myocardium at concentrations too low to affect normal tissue. To test this hypothesis, several parameters of myocardial contractile function were measured in nonischemic and ischemic segments of the left ventricle using small ultrasonic crystals.7 The dose-response relation of verapamil on nonischemic and ischemic myocardium was compared to that of propranolol, a potent beta-blocking agent known to decrease contractility.8 MethodsEighteen mongrel dogs of either sex (weight 20-30 kg) were anesthetized with sodium pentobarbital (20-25 mg/kg) and ventilated with room air through a cuffed endotracheal tube. Normal saline was infused at 50 ml/hr for the remainder of the experiment. The experimental preparation is shown diagrammatically in figure 1. A left lateral thoracotomy was performed through the fifth intercostal space and the heart was suspended in a pericardial cradle. The left anterior descending coronary artery (LAD) was dissected free at about 2 cm from its origin, usually above the first major diagonal branch, and prepared for later cannulation. Catheters were placed in the femoral artery and vein, Small stab incisions were made with a number 11 scalpel blade; two pairs of ultrasonic crystals (diameter 2 mm) were placed at a depth of 3-4 mm in the anterior left ventricle and secured with purse-string sutures. Each pair of crystals was separated by 1.5-2.0 cm of myocardium and aligned for optimum transmission of sound. One pair was placed outside the ischemic zone (normal segment) and the other within the zone of myocardium perfused by the LAD, but 1-2 cm distal to the level of LAD occlusion; i.e., that segment that would become ischemic after occlusion of the vessel (ischemic segment). The ultrasound crystals were made from 3 MHz piezoelectric crystal (LTZ 5, Transd...

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Effects of verapamil on infarct size following experimental coronary occlusion

Cited by 126 publications

References 0 publications

The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion‐induced arrhythmias in anaesthetized rats

The effects of verapamil, prenylamine, flunarizine and cinnarizine on coronary artery occlusion‐induced arrhythmias in anaesthetized rats

Calcium antagonistic and antiarrhythmic actions of CPU‐23, a substituted tetrahydroisoquinoline

Regional contractility. Selective depression of ischemic myocardium by verapamil.

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