A. J. Liedtke

We evaluated the consequences of excess free fatty acids (FFA) on mechanical and metabolic functions in globally perfused working swine hearts. In one group of eight hearts, treatments with heparin and 10% fat emulsion (Intralipid) produced a 3-to 5-fold elevation in serum FFA levels as contrasted with levels in 10 untreated hearts . At control flows, excess FFA caused declines in aortic pressure (-31.4%, P < 0.05), left ventricular systolic pressure (-24.8, P < 0.05), left ventricular work (-69.8%, P < 0.001), and epicardial motion (-57.8%, P < 0.001), together with an increase in myocardial oxygen consumption (+16.5%, P < 0.05) as compared to pretreatment values. Ischemia in untreated hearts also decreased mean aortic pressure (-46.2%, P < 0.005), left ventricular systolic pressure (-19.5%, P < 0.001), left ventricular max dp/dt (-27.9%, P < 0.001), left ventricular work (-49.1%, P < 0.025), myocardial oxygen consumption (-21.2%, P < 0.001) as compared with preischemic values. Excess FFA during ischemia resulted in even greater deteriorations in hemodynamic and metabolic functions. Tissue metabolites in the two groups of ischemic hearts were compared with those in six untreated hearts maintained at control flows. Tissue levels (mfiM/g dry weight) of long-chain acyl coenzyme A (CoA) esters were 70.1 6.5, 121.4 11.1 (P < 0.001), and 174.7 13.7 (P < 0.001) in control, ischemic with normal FFA, and ischemic with excess FFA hearts, respectively. Tissue fatty acyl carnitine levels (imiM/g dry) were 20.6 9.8, 380.1 51.6 (P< 0.001), and 685.1 115.7 (P< 0.001) in control, ischemic with normal FFA, and ischemic with excess FFA hearts, respectively. Thus, excess FFA caused significant impairments in cardiac function in association with elevations in tissue acyl CoA and acyl carnitine derivatives during ischemia. Accumulations of these products of fatty acid metabolism may interfere with enzyme functions and membrane transport systems.

The purpose of these studies was to characterize the rates of fatty acid oxidation in reperfused myocardium and test the influence of excess fatty acids (FA) on mechanical function in the extracorporeally perfused, working swine heart model. Seventeen animals were prepared. Eight were untreated (LOW FA group; serum FA averaged 0.55 +/- 0.07 mumol/ml) and nine received a constant infusion of 10% Intralipid with heparin to raise serum FA to about 1.4 +/- 0.21 mumol/ml (HIGH FA group). Coronary flow in both groups was held at aerobic levels for an equilibrium period of 40 minutes, acutely reduced regionally in the anterior descending circulation by 60% for 45 minutes, and acutely restored to aerobic levels for 60-minute reflow. Appreciable mechanical depression (-47 delta% from aerobic values; p less than 0.01) during reperfusion was noted in both groups. This was associated with modest reductions in myocardial oxygen consumption (p less than 0.05) and losses of total tissue carnitine stores (p at least less than 0.02). Reperfused myocardium showed a strong preference for and aerobic use of FA during reflow such that 14CO2 production from labeled palmitate exceeded preischemic levels (+89 delta% in LOW FA hearts; +111 delta% in HIGH FA hearts). This suggested relative preservation of restoration of certain elements in mitochondrial function during reflow. The findings argue for uncoupling between substrate metabolism and energy production, accelerated but useless energy drainage, or some impairment between energy transfer and function of contractile proteins as possible explanations for the persistent depression of mechanical function (stunning) during reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

To compare angiographically-determined coronary artery disease in diabetic patients with controls, 1,653 patients coming to cardiac catheterization were reviewed retrospectively to find 37 diabetic and 79 control patients matched for sex, age (+/- 3 years), and risk factors (hypertension, hyperlipidemia, and smoking). The severity of coronary artery disease was assessed using an angiographic grading system. The following results were obtained: 16 of 37 diabetic patients (43%) had three-vessel disease compared to 20 of 79 controls (25%). Seventy-six of 111 (68%) diabetic vessels were diseased compared to 110 of 237 control vessels (46%) (P less than 0.005). The total coronary score reflecting total extent of disease for diabetic patients was 371 (mean 10.0 +/- (SEM) compared to 594 for controls (mean 7.5 +/- 0.7, (P less than 0.01). Diabetic patients had a statistically similar number of diffusely diseased vessels as controls (28% vs 22%). There were only three of 76 diabetic vessels (4%) considered inoperable compared to seven of 110 (6%) control vessels. We conclude that diabetic patients with chest pain have more coronary artery disease than nondiabetics, but no more diffuse or inoperable disease.