An experimental approach is described to quantitate inhomogeneity in extracellular K concentration ([Ks ]out) in the presence of ischemia and to relate this inhomogeneity to the electrophysiologic changes. Extracellular potassium concentration and local direct-current electrograms from the same sites were measured in isolated perfused pig hearts with the use of multiple electrodes.Dispersion of [K' lout is described under three conditions: (1) during regional ischemia in the "central zone" and the "borderzone," (2) during global ischemia, and (3)

This study was performed to determine the reproducibility of the ionic and electrical changes associated with serial ischemic episodes. We used ion-selective and bipolar plunge electrodes to determine the changes in left ventricular extracellular potassium (

The ,3-adrenergic and calcium channel blocking agents are known to reduce heart rate and alter myocardial contractility. More recent evidence suggests that both agents affect the metabolic consequences of ischemia, independent of their effects on heart rate and contractility. We used a low-flow model of ischemia in swine with heart rate held constant by atrial pacing. Blood was shunted from the carotid artery to the left anterior descending coronary artery through a controlled-flow roller pump to assess the threshold flow for the rise in extracellular potassium ([K4Ie) and fall in extracellular pH (pHe) associated with ischemia during control situations and after the administration of either propranolol or verapamil. We also measured the changes in activation delay and contractility associated with graded flow reductions in the presence and absence of these drugs. We found that when heart rate is held constant, 1) verapamil shifts the threshold flow for [K4Ie and pH, to lower levels, but propranolol does not; 2) verapamil lessens activation delay, while propranolol aggravates the delay; and 3) verapamil reduces afterload and selectively depresses contractility in the reperfused ischemic zone. We conclude that the calcium channel blockers and the f-adrenergic-blocking agents have different effects and possibly different modes of action and should not be considered interchangeable when evaluating therapeutic options for patients with ischemic heart disease. (Circulation 1989;79: 939-947) T he ,3-adrenergic-blocking agents and the calcium channel blocking agents are both used in the treatment of patients with effortinduced ischemial2 due to coronary artery disease. The beneficial effects of these agents are attributed to their ability to reduce heart rate and contractility, thereby lessening the myocardial oxygen requirement. In addition, there is evidence to suggest that both the 8-adrenergic-and the calcium channel blocking agents may alter the metabolic consequences of reduced coronary blood flow independently of changes in heart rate or contractility.3,4 after the complete interruption of coronary blood flow5-8 been attributed to this mechanism. These effects would be expected to allow the myocardium to tolerate lower levels of coronary blood flow without becoming ischemic.Our recent studies9 have shown that the changes in extracellular potassium concentration ([K']e) and extracellular pH (pHe) are the most sensitive markers of ischemia when coronary blood flow is progressively reduced. As such, they provide a means for assessing the effects of physiologic and pharmacologic interventions on the coronary blood flow associated with the onset of ischemia. The present experiments were conducted to determine if propranolol or verapamil or both were capable of altering the coronary flow associated with the first change in[K4]e and pHe when heart rate was held constant. We also studied the effects of these drugs on myocardial activation during the progressive reduction of coronary blood flow because it is known th...

Our study demonstrates that the steady-state rate-dependent component of the slowing of intraventricular conduction induced by acute ischemia in the in situ porcine heart occurs in the absence of a rate-dependent component in the rise of [K+]e. Between rates of 90 and 150 beats/min, the rate dependence of the conduction slowing may be attributed to one or more potassium-independent factors such as the rate-dependent changes in resting membrane potential, in Vmax of the action potential upstroke, and in cell-to-cell uncoupling, which have been observed in other models of acute ischemia.

We examined the lg heavy chain variable region genes (Ig V(H) genes) expressed in biopsy specimens of 10 patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma. Eight expressed Ig V(H) genes of the V(H)4 group, indicating a bias toward expression of Ig V(H) genes of this subgroup. Sequence analyses of Ig V(H) genes isolated from any one lymphoma did not reveal evidence for intraclonal diversity. However, some lymphomas express Ig V(H) genes that apparently have undergone somatic diversification and selection. In addition, we found that the sequence encoding each examined third complementarity determining region most likely resulted from D-D fusion, a process that ordinarily contributes to the generation of a relatively small proportion of the Ig heavy chain genes expressed by normal adult B cells. The noted restriction in the use of Ig V(H) genes by AIDS-associated B-cell lymphomas suggests that antigenic stimulation contributes to lymphomagenesis in patients with AIDS.