Patrick H. Lehan

Ventricular Arrhythmias and K+ Transfer during Myocardial Ischemia and Intervention with Procaine Amide, Insulin, or Glucose Solution*

To assess the relation of ventricular arrhythmias to myocardial K(+) movement during ischemia, we placed an electrode catheter in the left anterior descending coronary artery for thrombus production in intact anesthetized dogs. (85)Kr injections distal to the thrombus permitted serial coronary blood flow measurements. Animals of Group I with a moderate flow reduction exhibited no arrhythmia or myocardial egress of K(+). In Group II, marked flow reduction was accompanied by an injury potential and loss of K(+) from the ischemic site, before and during ventricular tachycardia. Therapeutic interventions were performed in animals having the same degree of ischemia as Group II. Systemic procaine amide in Group III interrupted the tachycardia and egress of K(+), despite persistent ischemia. Group IV did not respond to intracoronary insulin with K(+) uptake, as did normal dogs, and progressed to fibrillation. During the production of hyperglycemia in Group V, myocardial loss of K(+) ceased with maintenance of sinus rhythm. Hemodynamic factors did not appear to have a major role in the genesis of the arrhythmia.Since intracoronary infusion of K(+) in normal dogs similarly altered repolarization and produced fibrillation, it would appear that during ischemia egress of K(+) before development of the arrhythmia indicates a major role of the ion in pathogenesis. This view is supported by the myocardial loss of K(+) and arrhythmia induced in normal dogs by strophanthidin and by the fact that pharmacologic regulation of K(+) loss is associated with correction of the arrhythmia, despite persistence of low blood flow.

Hemodynamic, electrocardiographic, and metabolic effects of fructose diphosphate on acute myocardial ischemia

The hemodynamic, electrocardiographic, and metabolic responses of dogs with acute myocardial ischemia to intravenous administration of fructose-1,6-diphosphate (FDP) were assessed. Analysis of the results (compared to dextrose control) revealed evidence of major improvement of LVEDP and cardiac output, significant decrease of the ST segment, and large increases of ATP and CP in the ischemic district and to a lesser degree in the normally perfused myocardium. These results indicate that FDP intervenes in the Embden-Meyerhof pathway not only as a high energy substrate but also as a metabolic regulator influencing the activity of phosphofructokinase and that of pyruvate kinase. FDP also stimulates glycolysis in dog erythrocytes and increases their ATP and 2-3 DPG content by a factor of 2. The most significant finding in these studies is that this biochemical intervention appears to restore the depressed activity of glycolysis in ischemic myocardium.

The fate of experimentally induced coronary artery thrombosis

Abstract The evolution of a thrombus in a coronary artery is uncertain. To evaluate this process, coronary artery thrombosis was induced in intact anesthetized dogs by passage of current through an electrode catheter in the circumflex or anterior descending branch of the left coronary artery. Twenty-five animals survived the immediate period after arterial occlusion, which was established angiographically. Survivors were placed in one of two groups depending upon the interval between thrombosis and spontaneous death or sacrifice: group I (1 to 17 days; 15 dogs) and group II (30 to 70 days; 10 dogs). Gross examination of the coronary arteries was performed post mortem in all dogs, with additional premortem angiographic studies in group II. At the time of death all dogs but 1 in group I showed continued evidence of significant obstructive thrombosis. In group II angiography and postmortem examination of the involved arteries indicated that within the second month after clot production sufficient changes occur within the thrombus to re-establish varying degrees of blood flow.

Hemodynamic effects of fructose 1,6-diphosphate in patients with normal and impaired left ventricular function☆☆☆

We compared the short-term hemodynamic effects of intravenous fructose 1,6-diphosphate (FDP) administration in patients with coronary artery disease. Hemodynamic measurements were performed before and after administration of FDP in two groups of patients: those with impaired left ventricular (LV) function, elevated LV end-diastolic pressures (LVEDP > or =12 mm Hg, n = 30), and those with normal LV function (LVEDP <12 mm Hg, n = 17). In those with impaired LV function, FDP induced a decrease in LVEDP from 22 +/- 1.31 to 16.73 +/- 1.46 mm Hg (p< 0.0001). The cardiac index increased (2.50 +/- 0.11 to 2.81 +/- 0.13 L/m2 [p < 0.0001]), as did the LV stroke work index (31.7 +/- 2.04 to 40.3 +/- 2.67 gm x m x m2 [p < 0.0001]). FDP induced no significant change in heart rate and mean aortic pressure. Pulmonary pressure and resistance declined (p<0.002 and p< 0.0001, respectively). Systemic vascular resistance decreased because of increased cardiac output and unchanged arterial pressure (p < 0.001). In those patients with normal baseline LVEDP (5.06 +/- 0.27 mm Hg), FDP decreased heart rate (p< 0.0001) and systemic and pulmonary resistance (p < 0.03 and p < 0.004, respectively), whereas LVEDP and mean aortic and pulmonary pressures remained unchanged. FDP moderately increased cardiac output (p < 0.05), stroke volume index, and LV stroke work index (p< 0.002 and p< 0.003, respectively). The observed improvement in LV function in those patients with elevated LV filling pressures is thought to be a result of an increased energy production by the Embden-Meyerhoff pathway and to act as a positive inotrope.

Congenital heart disease, deaf-mutism and associated somatic malformations occurring in several members of one family

Abstract A unique family is described in which the mother and four of her eight children have pulmonary stenosis. Two of the four affected children are deaf-mutes; one of these has, in addition to the pulmonary valvular stenosis, idiopathic hypertrophic subaortic stenosis. All the affected children had several associated somatic malformations. Genetic and nongenetic factors and their role in the development of the malformations are discussed. It is suggested that the cardiac defect is transmitted by a single non-sex-linked genetic factor (dominant autosomal inheritance). In the presence of a normal karyotype it appears that a single dose of either a point mutation, or a small deletion or translocation is the most likely cause.

Lipid and Carbohydrate Metabolism of Myocardium During the Biphasic Inotropic Response to Epinephrine

The metabolic response of the left ventricle to a 90 min regional infusion of 1-epinephrine (5 μg/min) was assessed in the intact anesthetized dog for 3 hr. The first hour was characterized by a rise in stroke output at constant filling pressure. Subsequently, contractility fell and there was release of K and PO4 ions as well as SGOT from the myocardium that was attributed to tissue injury. The myocardial RQ rose for the first hour, presumably due to glycogenolysis, since carbohydrate extraction from blood was unaltered. Production of lactate by the myocardium during the RQ rise occurred without ischemia, since blood flow (Kr85 method) and O2 uptake rose 10%. The proportionately greater increase in contractility was not consistent with “O2 wasting” as a basis for the injury. After 1 hr the RQ fell to levels consistent with predominant lipid utilization. However, FFA extraction declined and the oxidation, extraction and incorporation of palmitate-l-C14 into tissue lipid were diminished during hormone exhibition. Plasma triglyceride uptake, insignificant in controls, was enhanced during the 3 hr without a rise in arterial concentration. Oxidation of this lipid was insufficient to prevent a threefold triglyceride increment in the myocardium. The authors discuss a possible relationship of these metabolic alterations to the pathophysiologic response induced by epinephrine.

Coronary Blood Flow Measurements in the Presence of Arterial Obstruction

As an approach to delivery of inert gas to the myocardium in the presence of coronary artery obstruction, Kr85 in saline was injected into a catheter in the coronary venous system of intact anesthetized dogs. Isotope delivered at the level of the great cardiac vein was selectively localized in the region of myocardium subserved by the vein and the left anterior descending artery. Similarly, injection at the coronary sinus level was attended by localization of isotope to the area perfused by the circumflex branch of the left coronary artery. Precordial counting of isotope delivered in this retrograde manner yielded coronary blood flow values that closely corresponded to those derived from coronary arterial injection. Coronary thrombus formation in either of the major left coronary branches was reflected in substantial flow reductions when isotope was delivered via the artery distal to the thrombus. A similar flow decrement was observed when the gas was delivered via the corresponding venous site, while normal blood flow levels were derived from the nonischemic area. Application of the method to detection of coronary arterial obstruction in man is discussed.

Aneurysm of the membranous ventricular septum

Abstract Four cases of aneurysm of the membranous ventricular septum with associated ventricular septal defects diagnosed by left ventricular angiocardiography are reported and discussed in relation to the pertinent literature.

Retrograde Radioisotope Myocardial Perfusion Patterns in Dogs

A retrograde coronary vein injection technique for concentrating radioisotope in ischemic myocardial regions was evaluated in dogs. Potassium-43 in saline solution was injected into the coronary veins during complete closure of the coronary sinus. In the presence of coronary inflow obstruction, the venous potassium-43 was distributed mainly to the low pressure vessels in ischemic heart regions; i.e., the ratio of potassium-43 in the occluded-to-unoccluded areas ranged from 2:1 to 3:1 thirty seconds after retrograde injections. Krypton-85 in saline solution was injected under pressure into the coronary veins during partial closure of the coronary sinus. In the presence of inflow obstruction, the ratio of krypton-85 in the occluded- to-unoccluded areas ranged from 4:1 to 6:1 sixty seconds after retrograde injections; larger ratios may be expected after rapid washout of gas from the normally perfused region is nearly complete. Myocardial potassium-43 imaging techniques were applied to locate and measure the size of the ischemic heart region as a radioisotopic hot spot. Detection of hypoperfused areas of extremely small size may be accomplished by this technique.

Regression of intercoronary collateral vessels in mongrel dogs after coronary bypass grafting

Abstract Four dogs underwent direct revascularization of a chronically occluded circumflex artery with an internal mammary artery bypass graft. Preoperative coronary cineangiograms demonstrated well developed intercoronary collateral vessels supplying the circumflex arterial bed. Intraoperative measurements of retrograde circumflex arterial flow and pressure were consistent with the presence of large collateral vessels. Closed chest postoperative estimates of the potential collateral circulation were obtained by advancing a Judkins catheter to the internal mammary wedge position. The graft wedge pressure was equated to the retrograde circumflex pressure. After coronary bypass grafting, the interval coronary angiographic and hemodynamic studies indicated that well developed collateral vessels regressed within the first postoperative month to capacities in the range of those found in normal dogs.