The effects of verapamil, quiescence, and cardioplegia on calcium exchange and mechanical function in ischemic rabbit myocardium.

Bourdillon, Patrick D.V.; Poole‐Wilson, Philip A.

doi:10.1161/01.res.50.3.360

Cited by 195 publications

(35 citation statements)

References 35 publications

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“…In such an intact animal, isometric tension cannot be measured because the myocardial fibres shorten to eject blood, maintaining cardiac output and the integrity of the circulation. In isolated preparations the maximum rate of rise of tension is a suitable measure of contractility (Langer, Brady, Tan & Serena, 1975;Schulze, 1981;Bourdillon & Poole-Wilson, 1982); in the intact heart contractility can be measured by the maximum rate of rise of pressure, because it occurs during the isovolumic contraction period. In intact dogs we were able to assess maximum rate of rise of pressure from left ventricular pressure according to the principles laid down by Van den Bos, Elzinga, Westerhof & Noble (1973).…”

Section: Introductionmentioning

confidence: 99%

Cardiac action potential duration and contractility in the intact dog heart.

Drake-Holland¹,

Noble²,

Pieterse³

et al. 1983

The Journal of Physiology

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SUMMARY1. The maximum rate of rise of left ventricular pressure (DP) and action potential duration (a.p.d.) were measured in closed-chest anaesthetized dogs with atrioventricular dissociation and fl-adrenergic blockade. Right ventricular stimulation was carried out with protocols consisting of a conditioning 'priming' period and a test period.2. When a single test stimulus was introduced at varying intervals after the priming period, DP was found to be maximal at 800-1000 ms. With this single test stimulus fixed at the optimum, DP was found to be a variable inverse function of the a.p.d. of the same beat; no positive correlation could be found between DP and a.p.d.3. When a second test stimulus at the optimum interval was introduced after the first, the DP (DP2) was found to be strongly dependent on that elicited by the first test stimulus (DP1); the relationship was positive, linear, independent of the method used to vary DP, and independent of whether DP1 was depressed or potentiated. The slope of the relationship was less than 1I0 and the line passed through the point where DP2 = DP1; this is the point of continuous stimulation at the optimum interval in a steady state. 4. This result is consistent with the hypothesis that the coefficient relating DP1 to DP2, at constant a.p.d. of the first test pulse (AP1), is an index of the proportion of the activator of contraction stored during relaxation of test beat 1 which is released again on beat 2.5. In order to test the hypothesis that the remaining contractility depended on the action potential of test beat 1, AP1 was varied by changing the intervals between the priming stimuli.

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Section: Introductionmentioning

confidence: 99%

Cardiac action potential duration and contractility in the intact dog heart.

Drake-Holland¹,

Noble²,

Pieterse³

et al. 1983

The Journal of Physiology

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“…In view of the present findings on inward calcium currents, this beneficial action of prenylamine can be better understood. Several other calcium blocking agents have also been found to have such protective effects (Nayler et al, 1980;Bourdillon & Poole-Wilson, 1982;Watts et al, 1986). This is presumably due to the reduction of the calcium load imposed upon the cardiac cells, although direct protective actions by some of the drugs have also been considered (Higgins & Blackburn, 1984).…”

Section: Discussionmentioning

confidence: 99%

The effects of prenylamine on single ventricular myocytes of guinea‐pig

Shimoni

Posner²,

Spindler³

et al. 1988

British J Pharmacology

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1 The action of prenylamine, an antianginal drug, was studied in single ventricular guinea-pig myocytes. In concentrations of 10-50 pm, prenylamine significantly (P <0.01) shortened action potentials, and significantly (P < 0.001) reduced the inward calcium current by 29% to 76% (n = 7). This effect was also present in the presence of adrenoceptor-blockade (with phentolamine and propranolol), and was thus not due to indirect changes in endogenous catecholamine action. 2 Prenylamine did not affect the steady state level of current at the end of long pulses, and does therefore not act by changing time-dependent outward currents. Since the resting potential in the unclamped mode is unchanged during gross changes in action potential duration, it is also unlikely that there are any changes in the background, time-independent potassium conductance. 3 It is concluded that prenylamine has a direct effect on cardiac calcium channels, not mediated by adrenoceptor activation.

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“…Hence an ability of PN (and possibly other calcium antagonists too) to preserve flow to the subendocardial layer of the left ventricle, where the initial ischaemic damage occurs (Reimer et al, 1977;Regitz et al, 1984), could offer true protection to the myocardium. This might also explain why certain calcium antagonists have been found to offer cardioprotection only when administered before the ischaemic event (Watts et al, 1980;Bourdillon & Poole-Wilson, 1982). Once the subendocardial vessels have already become constricted, drug access to these regions may become limited, and their success as cardioprotective agents accordingly reduced.…”

Section: Discussionmentioning

confidence: 99%

“…Previous experimental studies have shown that a number of calcium antagonists can protect the heart against ischaemic damage, particularly when applied before the ischaemic insult (Nayler et al, 1980, Watts et al, 1980, Bourdillon & Poole-Wilson, 1982. However, the exact mechanism(s) involved in this protection' remain(s) unclear.…”

Section: Introductionmentioning

confidence: 99%

Cardioprotection by the calcium antagonist PN 200‐110 in the absence and presence of cardiodepression

Cook

Hof

1985

British J Pharmacology

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The globally‐ischaemic Langendorff rabbit heart model has been used to study the cardioprotective effects of the dihydropyridine PN 200‐110 (PN) at two doses, one having no negative inotropic effect and a higher dose causing a 62 ± 5% reduction in contractility. Following 45 min no‐flow global ischaemia, recovery was monitored for a period of 90 min reperfusion. Hearts were paced at a constant rate throughout experiments. Contractile force and coronary flow were recorded continuously. Tracer microspheres were injected at regular intervals to assess regional flow distributions, drill biopsies were taken to determine tissue high energy phosphate content, and enzyme leakage in the coronary effluent measured during the first 15 min of reperfusion. Untreated hearts recovered 21 ±2% of their initial contractile force and flow to all heart regions was reduced. In particular, endocardial flow fell to 20% of its pre‐ischaemic level, with the ratio of flow to the endocardium (endo)/epicardium (epi) decreasing from ca. 1.0 to 0.4. Hearts treated with 2 × 10−8 M PN (included in the perfusate from 30 min before ischaemia until 30 min after ischaemia) recovered 49 ± 2% of their initial, pretreatment contractile force, and following the ischaemia the endo/epi ratio was not significantly changed from the pre‐ischaemic value. The lower PN dose (3 × 10−10 M) afforded a lesser degree of protection, contractility recovering to 29 ± 4% of the initial level, with an endo/epi ratio of 0.7 after 90 min reperfusion. The two PN doses afforded a similar degree of protection against enzyme leakage which was in both cases significantly less than in untreated hearts. Myocardial ATP and creatine phosphate content was markedly reduced by the ischaemic episode. Neither PN dose modified this depletion. These results suggest that whilst cardiodepression may well offer protection against ischaemic damage, this is not the sole mechanism wherby PN (and possibly other calcium antagonists) can protect the heart. Preservation of blood flow to the inner layers of the left ventricular wall is likely to be one of the major factors underlying the enhanced recovery shown by PN.

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The effects of verapamil, quiescence, and cardioplegia on calcium exchange and mechanical function in ischemic rabbit myocardium.

Cited by 195 publications

References 35 publications

Cardiac action potential duration and contractility in the intact dog heart.

Cardiac action potential duration and contractility in the intact dog heart.

The effects of prenylamine on single ventricular myocytes of guinea‐pig

Cardioprotection by the calcium antagonist PN 200‐110 in the absence and presence of cardiodepression

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