Oxygen consumption, myocardial, and

Verapamil. Verapamil hydrochloride is a pbenyl alkyl amine and is considered the prototype of the Class I calcium channel blockers. Verapamil is also a potent inhibitor of coronary artery spasm and is useful in Prinzmetal s angina and in unstable angina at rest. Verapamil produces negative chronotropic and inotropic effects. These two actions reduce myocardial oxygen consumption and probably account for the effectiveness of verapamil in chronic stable effort angina (98,99). Moreover, verapamil is an effective antihypertensive agent. 

Newer experimental agents - The dimethyl quaternary analog of propranolol, UM-272 (SC-27761, 25). a non beta-blocker, has been shown to reduce myocardial oxygen consumption and infarct size in dogs, presumably via a non-specific reduc-... 

Equally as important, and potentially more clinically relevant, are the indirect mechanisms responsible for the antiarrhythmic activity of calcium inhibitory agents, including coronary vasodilation and subsequent increases in coronary artery blood flow (47, 114, 124, 157) decreased cardiac contractility, metabolism, and arterial vasodilation resulting in decreases in myocardial oxygen consumption and wall tension (92) and reflex alterations in autonomic regulation of heart rateToverdrive supression) and AV conduction (114) ... 

Nitrates primarily decrease venous tone that results in increased coronary perfusion. In addition, venodilation results in decreased filling of the heart, and decreased preload. Afterload may also be decreased, proportionate with the degree of arterial dilation of the particular drug. The net result is a decrease in myocardial stretch leading to increased cardiac output (due to Starling s law), decreased myocardial oxygen consumption, and an increase in coronary perfusion. 

Sulmazole (AR-L 115) (37), an imidazopyridine derivative, increased dp/dt max. by 58% and heart rate by 12 beats/min in anesthetized cats after 1 mg/kg i.v. Systolic blood pressure was decreased by 13 mm Hg.l42 Oral administration augmented dp/dt max. up to 92% for 5 to 12 hours in conscious dogs.143 Despite similar PDE-inhibitory activity of 37 and theophylline, it seems likely that effects other than PDE-inhibi-tion contribute to the positive inotropic action.144 Measurement of the effect of 21 on relations between free Ca++, bound Ca ", and ATPase activity of dog cardiac myofibrils indicates that the positive inotropic actions may involve direct activation of myofibrils by an increased affinity of thin filament receptors for Ca++.145 Several clinical studies in heart failure showed that in patients with congestive cardiomyopathy and with coronary artery disease, 22 improved hemodynamics and regional wall motion via decrease in pre- and afterload and Increase in contractility, myocardial oxygen consumption and coronary sinus flow, with no myocardial ischemia.14 149... 

Goto, Y., Futaki, S., Kawaguchi, O. et al., Coupling between regional myocardial oxygen consumption and contraction under altered preload and afterload, /. Am. Coll Cardiol, 21, 1522-1531,... 

Figure 7. Effect of dipyridamole on the interrelationships between myocardial oxygen consumption and coronary blood flow (A), myocardial oxygen consumption and pericardial infusate concentration of adenosine (B), and pericardial infusate concentration of adenosine and coronary blood flow (C) in the anesthetized open-chest untreated dog (solid lines) during basal conditions (open squares) and interventions (open stars), such as aortic constriction, calcium infusion, norepinephrine infusion, and atrial pacing. The closed squares and stars represent the control and experimental procedures, respectively, when carried out in the presence of dipyridamole (dotted lines). Note that in A and B, dipyridamole shifts the curves to the left (greater flow for the same oxygen consumption). In C, the close parallelism between adenosine release and coronary blood flow is unaffected by dipyridamole. (Reproduced by permission of Martinus Nijhoff publishing, Boston, The Regulatory Function of Adenosine, In Berne RM, Rail TW, Rubio R (eds), p. 293,1983).

Rao MR, Liang MD 1980 Effects of protocatechuic acid on myocardial oxygen consumption and tolerance to anoxia in animals. Chung-Kuo Yao Li Hsueh Pao 1 95-99... 

Amiodarone dilates arteriolar vascular smooth muscle, especiady coronary arteries, and thus exhibits antianginal effects. Its effects on the peripheral vasculature to decrease resistance leads to a decrease in left ventricular stroke work and a decrease in myocardial oxygen consumption. The dmg rarely produces hypotension that requires discontinuation of the dmg (1,2). 

The pharmacological mechanisms of action of NO donors that contribute to their benefit in coronary artery disease, congestive heart failure, and hypertension are listed in Table 11.1. These actions can be grouped into five categories vasodilation, decrease in myocardial oxygen consumption, improvement in hemodynamic performance,... 

Buxton DB, Nienaber CA, Luxen A, Ratib O, Hansen H, Phelps ME et al. Noninvasive quantitation of regional myocardial oxygen consumption in vivo with [1-1 ICjacetate and dynamic positron emission tomography. Circulation 1989 79 134-142... 

Since Kantrovitz et al. described the concept of counterpulsation in 1968 [3], the lABP has been the mainstay for temporarily augmenting the cardiac output and improving hemodynamics in acutely decompensated refractory HF [4, 5]. lABP use has been shown to reduce heart rate, left ventricular end-diastolic pressure, mean left atrial pressure, afterload, and myocardial oxygen consumption by at least 20-30%. The lABP also modestly increases coronary perfusion pressure and decreases the right atrial pressure, pulmonary artery pressure, and pulmonary vascular resistance [6]. 

All of the aforementioned beneficial effects of the /3-blockers are caused by the blockade of /3i-adrenoceptors. The beneficial effect of /3-blockers in the treatment of angina is largely caused by the reduction of heart rate and the concomitant decrease in myocardial oxygen consumption, thus improving the imbalance between oxygen supply and consumption which underlies myocardial ischaemia. 

Verapamil and diltiazem as for the dihydropy-ridines. In addition reduction in heart rate reduced myocardial oxygen consumption. 

Esmolol is used in the treatment of supraventricular tachyarrhythmias for rapid control of ventricular rate and reduction of myocardial oxygen consumption. Discontinuation of administration is followed by a rapid reversal of its pharmacological effects because of es-molol s rapid hydrolysis by plasma esterases. 

The associated initial release of catecholamines may result in an excessive pressor response and stimulation of cardiac force and pacemaker activity. The resulting increase in myocardial oxygen consumption in a patient with ischemic heart disease may lead to ischemic pain (angina pectoris). Patients in a state of circulatory shock probably should not be administered bretylium because of its delayed sympatholytic action. 

Amiodarone relaxes vascular smooth muscle one of its most prominent effects is on the coronary circulation, reducing coronary vascular resistance and improving regional myocardial blood flow. In addition, its effects on the peripheral vascular bed lead to a decrease in left ventricular stroke work and myocardial oxygen consumption. Therefore, amiodarone improves the relationship between myocardial oxygen demand and oxygen supply. IV administration may be associated with profound hypotension requiring volume expansion therapy. 

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