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J M Capasso

Publications and source records attributed to J M Capasso.

111 records · Page 7Linked to original sources

Age-related differences in excitation-contraction coupling in rat papillary muscle.

To investigate the possible role of an alteration in excitation-contraction coupling during development, aging and senescence we compared simultaneously recorded mechanical and electrical activity of left ventricular papillary muscles from 3, 6, 12, and 24-month-old male rats. In addition, the effects of calcium and verapamil on excitation-contraction coupling were evaluated. We recorded transmembrane action potentials during both isometric and isotonic contractions. At al external bath calcium = 2.4 mM, action potential duration at 75% complete repolarization (APD75) was significantly prolonged as a function of age (3 mo = 28.2 +/- 2.7; 6 mo = 29.5 +/- 2.6; 12 mo = 49.5 +/- 5.6; 24 mo = 121 +/- 8.5 msec) while peak developed tension (DT) was not significantly altered (3 mo = 5.13 +/- 0.53; 6 mo = 4.75 +/- 0.53; 12 mo = 7.26 +/- 0.51; 24 mo = 6.01 +/- 0.67 g/mm2). The correlation coefficient (r value) for APD75 and DT was strong for 3-month-old animals (4 = 0.99) but weakened as a function of age (6 mo = 0.93; 12 mo = 0.81; 24 mo = 0.57). Similar results were observed when APD75 was correlated with time-to-peak tension (TPT) (3 mo = 0.95; 6 mo = 0.98; 12 mo = 0.85; 24 mo = 0.68), time-to-one-half relaxation (T1/2R) 3 mo = 0.91; 6 mo = 0.97; 12 mo = 0.85; 24 mo = 0.81) and time to peak shortening (TPS) (3 mo = 0.89; 6 mo = 0.81; 12 mo = 0.82; 24 mo = 0.51). Correlations between action potential duration and contractile parameters became weak in all age groups upon the addition of verapamil (V). The correlation between APD75 and DT for 3-month-old animals decreased by 34% upon the addition of V while a 70% decrease was seen in 24-month-old animals. Similar results were seen when APD75 was correlated with TPT, T1/2R and TPS when V was added to the perfusate. Our results indicate that excitation-contraction coupling, as evidence by alterations in not only the contractile apparatus but also in the surface membrane, may be altered in ventricular muscle as in function of age.

Action Potentials↗

Sex differences in myocardial contractility in the rat.

We examined the intrinsic contractile performance of papillary muscles removed from the left ventricle of male and female Wistar rats. Muscles were studied isometrically and isotonically, stimulated at 0.1 Hz, perfused with Tyrode's solution having an external calcium concentration = 2.4 and maintained at 30 degrees C. In addition, we examined muscle response to changes in external calcium, added norepinephrine or verapamil and alterations in contraction frequency. No significant change in peak isometric development tension was observed between male and female preparations. However, muscles from male rats showed a significantly greater isometric time-to-peak tension and time to 1/2 relaxation with a depression of both the maximum rate of tension rise and maximum rate of tension decay. Isotonically, although peak shortening showed no difference between male and female preparations, the maximum velocities of shortening and relaxation were significantly depressed in muscles from male rats. Muscles from male animals also displayed significant prolongation of the time-to-peak shortening and time-to-peak velocity of shortening. These differences in papillary muscle performance were found over a wide range of muscle lengths, stimulus frequencies and bath concentrations of calcium, norepinephrine and verapamil. Thus differences in the intrinsic contractile performance between papillary muscle from male and female rats have been characterized.

Animals↗

Renal hypertensive hypertrophy in the rat: a substrate for arrhythmogenicity.

We investigated the ability of ouabain to produce lethal arrhythmias in rats with myocardial hypertrophy resulting from chronic renal hypertension. A gradual pressure overload was produced in female Wistar rats by left renal artery stenosis (two kidney, one clip, Goldblatt hypertension). Hypertension (systolic blood pressure greater than 150 mm Hg) developed within three weeks after clipping of the left renal artery and blood pressure continued to increase for the next five weeks. At ten weeks after the onset of hypertension animals were anesthetized with sodium pentobarbital (40 mg/kg) and artificially ventilated with room air while ECG was continually monitored and recorded. Continuous infusion of ouabain was maintained (0.7 mg/kg/min) through the inferior vena cava. Body weight and heart rate of control animals (C) was not significantly different from hypertensive (H) values, while systolic blood pressure in animals hypertensive for ten weeks was considerably greater (187 +/- 8.4 mm Hg) than their age-matched normotensive counterparts (123 +/- 6.0 mm Hg). Heart weight in hypertensive animals was elevated by 69% +/- 2.5 by time of study. Serological evaluation of both groups of animals revealed no significant differences in electrolytes and blood gases while significant differences were noted in glucose, BUN and creatinine. The average time to the first premature ventricular contraction was significantly shorter in H animals (3.5 +/- 0.2 min) when compared to C rats (6.0 +/- 0.2 min). The average time to ventricular tachycardia, ventricular fibrillation and death were also significantly shorter in H rats when compared to C animals (7.5 +/- 0.6 vs. 13.5 +/- 0.3; 13.5 +/- 0.5 vs. 21.0 +/- 0.5; 15.6 +/- 0.4 vs. 24.0 +/- 0.6 min). Thus, the hypertensive hypertrophied myocardium displays an increased propensity for lethal cardiac arrhythmias due to ouabain.

Animals↗