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Biomedical subjects

M B Knudson

Publications and source records attributed to M B Knudson.

6 recordsLinked to original sources

Cardiac contractility, cAMP concentration, cAMP-dependent protein kinase, and phosphorylase activation during acute pressure overload.

The relationship between increases in myocardial contractility and cAMP and protein kinase activity were studied for hearts of normal rats and those with altered sympathectic capacity produced by the combined treatments of adrenalectomy, and 6-hydroxydopamine and propranolol injections. Increases in myocardial contractility, evaluated from intra-ventricular pressure changes, were produced by occlusion of the ascending aorta for 15, 20, or 25 s. Resting peak left ventricular pressure and the rate of rise of left ventricular pressure were lower (P less than 0.05) in sympathectomized animals, however, aortic occlusion abolished these differences. Time to peak tension and the relationship between end-diastolic pressure and developed pressure were unchanged by sympathectomy. ATP and CP concentrations in freeze clamped samples of the myocardium were lower (P less than 0.05) in both groups after aortic occlusion whereas lactate was elevated (P less than 0.05). Sympathectomy delayed and reduced the magnitude of the increase in the phosphorylase a/a + b ratio produced by aortic occlusion. Myocardial cAMP concentration was increased in the normal rats but decreased in sympathectomized animals after aortic occlusion. cAMP-dependent protein kinase activity followed the pattern of cAMP. The results demonstrate that heart possesses the capacity to increase its contractility to an acute, short-term overload even when devoid of sympathetic control.

Adrenal Medulla

Orthogonal ventricular electrogram sensing.

Inappropriate demand pacing is most commonly due to improper ventricular electrogram sensing. Filters and programmable sensitivities improve electrogram sensing of conducted beats, but paced electrograms cannot be sensed by conventional unipolar or bipolar systems. A permanent pacing lead with a standard tip electrode and three orthogonal 0.8 mm2 sensing electrodes located circumferentially 2 cm proximal to the pacing tip was tested in 22 patients. The tip electrode was placed in the right ventricular apex in standard pacing position. Orthogonal electrodes were not in contact with ventricular myocardium. Orthogonal ventricular electrograms from 54 electrode pairs were compared with unipolar tip electrograms during conducted rhythms and paced beats. Tip ventricular electrograms averaged 12.8 mV with 3.04 mVT waves. Orthogonally recorded ventricular electrograms during conducted beats averaged 8.86 mV with T waves of 1.57 mV. During pacing, tip ventricular electrograms were obscured by the stimulus artifact and repolarization events. Orthogonal ventricular electrograms, however, demonstrated small discrete stimuli of 1.99 mV followed by discrete ventricular electrograms of 9.19 mV and T waves of 1.9 mV. Orthogonal ventricular electrograms compared favorably with contacting tip electrograms during conducted beats and provided a redundant sensing capability. During pacing, orthogonal ventricular electrograms allowed the capability for capture verification. A new pacing catheter allows for improved ventricular electrogram sensing and capture verification.

Arrhythmias, Cardiac

Exercise-induced glycogenolysis in sympathectomized rats.

The role of the adrenergic system in regulating glycogenolysis during exercise was studied in rats. Alterations in the adrenergic system were produced by injections of 6-hydroxydopamine (6-OHD), surgical removal of the adrenal medulla (ADMX), or the combination of ADMX and 6-OHD injection. Exercise was treadmill running at 22 m/min for 60 min. Colonic temperature averaged 2.8 degrees C higher in the exercised than control rats. Exercise reduced the glycogen of the liver and skeletal muscles of all groups. The glycogen concentrations of the soleus and red portion of the gastrocnemius muscles of the ADMX and ADMX-6-OHD groups were about 3.8 and 2.5 times higher after exercise than those of the normal-exercised rats. Glycogen depletion of the white portion of the gastrocnemius muscle was similar for all exercised groups. 6-OHD treatment depleted the catecholamines of the myocardium. These results demonstrate that glycogen depletion during exercise occurs in rats devoid of adrenergic control. However, differences between types of skeletal muscle suggest that factors other than the adrenergic system may be involved in controlling glycogen metabolism during exercise.

Adrenal Medulla

Systolic time intervals in induced atrial fibrillation in the dog: effects of ectopic ventricular activation.

Electrocardiogram, atrial electrogram, phonocardiogram, aortic pressure, and left ventricular pressure were recorded during periods of induced atrial fibrillation in dogs anesthetized with a combination of morphine sulfate and pentobarbital sodium. Data were accumulated by selecting 50 cardiac cycles which terminated in ectopic ventricular electrical complexes, and comparing systolic time intervals (STI) following these beats with STI Following 50 normal ventricular complexes. Ectopic ventricular activation prolonged left ventricular pre-ejection period and external isovolumic contraction time, and reduced duration of left ventricular ejection time. These events resemble changes in STI observed following induction of atrial fibrillation from a sinus rhythm, but they are of significantly greater magnitude than the effects of atrial fibrillation alone.

Animals

Muscle metabolism and cardiac function of the myopathic hamster following training.

The effect of 18 wk of treadmill running on skeletal muscle metabolism and myocardial function of normal and myopathic hamsters was examined. BIO 14.6 hamsters could tolerate an exercise intensity of about 18 m/min for 40 min, 5 days/wk. Further increases in speed or number of bouts per day resulted in a falloff in performance. Normal hamsters could tolerate higher speeds and longer exercise bouts. Exercise did not change the severity of lesions of either the heart or skeletal muscle of the myopathic hamsters. A training effect was evidenced by increased succinate dehydrogenase activity in the soleus muscle. Cardiac function was evaluated as contractility measured from left ventricular pressure curves and expressed as (dP/dt)/kP. The results suggested that cardiac contractility was not as severely depressed in the trained BIO 14.6 strain of hamsters as in nontrained controls. However, (dP/dt)/kP was lower in the trained myopathic animals than in normal hamsters. ATP, CP, and glycogen levels were lower in myopathic hamsters with the lowest values occurring in the trained group. These data demonstrate that the BIO 14.6 strain of hamster can tolerate exercise training and that such training may have a positive effect on cardiac function.

Animals

Systolic time intervals in induced atrial fibrillation in the dog.

The effect of induced atrial fibrillation on ventricular performance in the dog as measured by changes in the systolic time intervals (STI), was investigated. Atrial fibrillation was induced by enhancement of vagal tone with morphine sulfate, followed by direct mechanical stimulation of the atrium. Dogs received 15 mg. per kilogram of morphine sulfate subcutaneously, followed by 3 mg. per kilogram of pentobarbital sodium. ECG, atrial electrogram, phonocardiogram, and direct arterial blood pressure were recorded during periods of sinus rhythm and during periods of induced atrial fibrillation. Data were analyzed by selecting 20 representative cardiac cycles from each condition in each of 15 dogs. Cycles were selected so that the broadest spectrum of rates was examined for each animal. Three hundred cycles were examined from each condition, or a total of 600 cycles. Heart rate (HR), left ventricular end-diastolic pressure, and aortic end-diastolic pressure were unchanged during atrial fibrillation. The left ventricular pre-ejection period (LVPEP), externally derived isovolumic contraction time (EICT), and total mechanical systole (S1-S2 interval) were all found to increase significantly in duration after the induction of atrial fibrillation. The left ventricular ejection time (LVET) and the electromechanical delay (Q-S1 interval) were significantly decreased in duration following the induction of atrial fibrillation.

Animals