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)
Fatty acid metabolites (long-chain esters of CoA and carnitine) which collect in ischemic myocardium can form amphiphiles capable of disrupting subcellular performance. It is important to document the role of these amphiphiles in intact tissue. D-Octanoylcarnitine was chosen because of its previously described effects on inhibiting palmitoylcarnitine transferase (PCT-II) in in vitro and in vivo liver preparations. This inhibition will shift tissue levels of CoA and carnitine intermediates and thus alter amphiphile levels. The compound's actions in cardiac muscle are unknown. Dose response curves were developed in intact hearts to test the influence of D-octanoylcarnitine at pharmacological concentrations. Measurements were obtained in working, extracorporeally perfused, swine hearts. Drug was administered either systemically (IV) or via direct intracoronary (IC) infusions into the left anterior descending coronary circulation. Excess fatty acids were provided to ensure adequate fatty acid substrate for oxidation. Coronary flow was controlled at aerobic levels. Systemic administration of D-octanoylcarnitine (0.8-6.8 mM) resulted in transient peripheral hypotension which caused correlative decreases in 14CO2 production from labeled palmitate. Infusion of D-octanoylcarnitine (0.5-3.9 mM) IC did not cause appreciable hypotension and was not associated with suppression of fatty acid oxidation. No build-up of carnitine esters was noted in treated hearts but acyl CoA levels were reduced (p less than or equal to 0.002). This latter finding was modestly related to increasing dose schedule of the compound in the IC group. The lack of suppression in fatty acid oxidation argues against significant inhibition of PCT II and lessens the attractiveness of using D-octanoylcarnitine in intact myocardium to selectively block fatty acid utilization at this locus.
A decline in the heart muscle strength is a well-recognized aspect of normal aging. Nonetheless, the resting heart rate (HR) in developing adults appears to be unchanged. The aim of this study was to determine if HR recovery after exercise is influenced by age. Healthy male and female volunteers, aged 12-61 years, were divided into two groups. The first group included participants younger than 30 (18.8 +/- 4.15), and the second group included individuals that were older than 30 (50.0 +/- 8.56 years). After resting HR in sitting position was recorded, the participants were asked to perform a basic step platform exercise for 3 minutes at a consistent pace of 14 lifts per minute. The HR was measured again right after the completion of the exercise and one more time 10 minutes post exercise. Resting HR recorded in the study was 77.7+/-10.22 beats/min. We observed 41% increase in HR immediately after the completion of the exercise (p=0.001). Only partial recovery was detected after 10 min of rest as HR remained 13% elevated compared to the resting baseline (p=0.005). Remarkably, there was no significant difference between two age groups in the resting HR, maximal HR, or HR change during recovery period (p>0.05). Our data suggest that the age alone does not define HR parameters measured here. Other contributors, like BMI and physical fitness are discussed. The findings of this study may be used for development of community-based strategies for improvement in health and life quality for increasingly aging population.
The body position is influencing multiple physiological functions, including blood pressure, lung capacity, and mood. A previous study indicated significant difference in the HR measures in sitting, prone, and supine position if the breathing pace is normalized to the same frequency (Watanabe at al. 2007). The aim of the study was to determine if heart rate is different in sitting, prone, and supine positions under more common circumstances, when the breathing pattern is not unnaturally adjusted. Heart rates were measured for 1 min in 12 male and female healthy volunteers (average age of those was 35.8+/-17.58) after they were instructed to remain in a seated position for 10 min, and then after 5 minutes in prone and supine positions. Participants kept the same posture during HR measures. Average HR in the sitting position recorded in the study was 77.7+/-10.22 beats/min; HR in prone position was 78.5+/-8.32 beats/min; and HR in supine position was 74.8+/-5.61 beats/min. There were no statistically significant differences between group means as determined by one-way ANOVA (F (2,30) = 0.89, p = .42). Our data indicate that the sitting, prone, and supine position have similar effect on HR if breathing pattern is not adjusted. As prone, supine, or sitting positions are commonly accepted by patients undergoing manual therapy, our data may have an important implication for efficient management of such patients. The finding of this study also can be used for development of better treatment strategies of the individuals that are exhibiting various degree of circulatory compromise.
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