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Myocardial cell pH was measured with 5, 5 dimethyl-2, 4-oxazolidinedione (DMO) in intact anesthetized dogs by a transient indicator dilution technique. Bolus injections of labeled DMO, vascular, extracellular and water indicators were made into the left anterior descending coronary artery, and blood samples were collected from the great cardiac vein. The steady state distribution of DMO between cells and plasma was calculated from the mean transit times of the indicator. Normal myocardial cell pH averaged 6.94 and changed by 58% of the concomitant alterations in plasma pH after infusions of acid or alkali. Myocardial ischemia induced by inflation of a balloon tip catheter in the left anterior descending coronary artery resulted in progressive decreases in cell pH to 6.59 by 1 hour. Infusions of sodium carbonate diminished intracellular acidosis. Hemodynamic studies during 4 hours of ischemia with blood pH at 7.55 to 7.60 indicated a significantly reduced left ventricular end-diastolic pressure and increased stroke volume by comparison with findings in animals given infusions of saline solution. Ventriculograms revealed improved wall motion in the ischemic segment after infusion of alkali. Precordial mapping showed a significant reduction in the number of leads with S-T segment elevation as well as in the sum of S-T segment elevations, but R wave amplitudes did not differ from those in control studies. Calculations of extracellular space, tissue water and cation content revealed a reduced gain of cell sodium ion and loss of cell potassium ion during ischemia after alkali treatment. The latter may account for the S-T segment responses, whereas enhanced ventricular performance may be related to reduced competition of hydrogen ion with calcium ion for binding sites on contractile protein.

The toxic effects of acute or chronic use of alcohol on cerebral and hepatic function have long been recognized, but it has been thought that the heart was not similarly affected. This study reexamines this traditional thought and indicates that ethyl alcohol may have chronic toxic effects on the cardiovascular system.

In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium. To evaluate myocardial lipid metabolism, [1-(14)C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced (14)CO(2) production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [(14)C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic.

The current approach to cardiac disease recognizes that the cardiovascular problems of diabetic patients have both a coronary artery atherosclerotic component and an independent myocardial component. The presence of the myocardial component has become more apparent in recent years, and a full understanding of the balance between the two components is necessary for proper treatment of the cardiac problems of patients with diabetes.

While conduction disturbances and arrhythmias are seen frequently in alcoholic cardiomyopathy, the specific relationship of these changes to ethyl alcohol has been unclear. To investigate the long-term effects of ethanol upon cardiac conduction, alcoholism was induced in 11 male mongrel dogs for 7 to 33 (mean 14.4) months by feeding up to 36 per cent of total daily calories as ethanol while adequate nutrition was maintained. His and left bundle branch electrograms in the intact anesthetized animals were recorded along with high-speed, high-frequency ECG's. While resting left ventricular pressures, volumes, and stroke outputs were normal, H-Q time was prolonged in the alcoholic animals drinking for longer than one year (35 +/- 3 msec., normals 26 +/- 1 msec.-P less than 0.001). QRS widening (to 80 +/- 4 msec.) was also evident after one year as compared with normals (62 +/- 2 msec.-P less than 0.001), and both H-Q and QRS alterations correlated with duration of intake. These changes were less after shorter ingestion periods, could not be reproduced in normals by acute ethanol infusion, and were not associated with ventricular hypertrophy, inflammation, or necrosis. No abnormalities of atrial conduction were noted. Morphologic correlates of the conduction abnormalities included accumulation of Alcian Blue-positive interstitial material as well as dilatation and localized swelling of the nonspecialized region of the intercalated discs in ventricular muscle and Purkinje fibers. Thus, prolonged ethanol intake in the absence of evident malnutrition resulted in demonstrable intraventricular conduction abnormalities and morphologic alterations which were related to duration of ingestion, consistent with a cumulative toxic effect of ethanol.

Potassium chloride infusion into the left anterior descending coronary artery induces a sequence of events analogous to those occurring during acute transmural ischemia. These include ST elevation, intramural conduction delay, ventricular techyarrhythmias and fibrillation. The influence of antiarrhythmic agents in an intact anesthetized canine model have not previously been tested. We have evaluated the efficacy of lidocaine, procaine amide and practolol in animals during regional hyperkalemia. In the untreated, only 9% survided a 20 minute observation period. All three treatment groups exhibited a reduced incidence of tachycardia and 74% survived the test period. In each treatment group this was associated with a further prolongation of intramural conduction time in the affected wall. This antiarrhythmic efficacy, thought possibly to be due to transformation of unidirectional to bidirectional block, supports the view that modulation of transcellular potassium activity contributes to the control of ischemic arrhythmias.