The influence of atrial fibrillation on coronary circulation was studied in 21 anesthetized open-chest dogs. Atrial fibrillation was induced either by local application of acetylcholine (10% in normal saline) on the left atrial appendage or by electric stimulation (2-7 volts, 2 ms, 50 Hz). When atrial fibrillation was induced (n = 10), mean aortic pressure fell and heart rate rose significantly; coronary blood flow (CBF) remained unchanged (78 +/- 6 vs. 75 +/- 5 ml/min X 100 g) while coronary vascular resistance (CVR) (1.16 +/- 0.05 vs. 0.87 +/- 0.07 [m Hg X min X 100 gl/ml [RU], p less than 0.0001) and sinus oxygen saturation (26 +/- 2 vs. 22 +/- 1%, p less than 0.05) decreased. Following the application of carbochromen (5 mg/kg in 3 min i.v.) resulting in maximal coronary dilatation, atrial fibrillation resulted in a reduction in CBF (311 +/- 48 vs. 205 +/- 30 ml/min X 100 g, p less than 0.01) and coronary sinus oxygen saturation (65 +/- 6 vs. 42 +/- 6%, p less than 0.01), while CVR (0.27 +/- 0.03 vs. 0.37 +/- 0.04 RU, p less than 0.0001) was 38 +/- 8% (p less than 0.0005) higher during atrial fibrillation than at sinus rhythm. When hearts were paced to a rate which was identical to the average heart rate at atrial fibrillation (n = 11), CBF (92 vs. 125 +/- 14 ml/min X 100 g, p less than 0.001) and sinus oxygen saturation (24 +/- 2 vs. 30 +/- 2%, p less than 0.0025) were higher and CVR (1.16 +/- 0.11 vs. 0.97 +/- 0.10 RU, p less than 0.0005) lower than during atrial fibrillation; during maximal coronary dilatation by carbochromen, pacing also resulted in a higher CBF (233 +/- 24 vs. 168 +/- 16 ml/min X 100 g, p less than 0.0005) and sinus oxygen saturation (70 +/- 3 vs. 57 +/- 2%, p less than 0.0005), while CVR (0.25 +/- 0.02 vs. 0.46 +/- 0.02 RU, p less than 0.0005) was lower than during atrial fibrillation. Thus atrial fibrillation results in a decrease in coronary vascular resistance but an increase in coronary oxygen extraction. When heart rate is controlled, the vasoconstrictor effect of atrial fibrillation becomes unmasked. Coronary vasoconstriction during atrial fibrillation appears to be greater during maximal coronary dilatation than during control.

Animals↗

PubMedDate not supplied

Electrophysiological interactions between carbachol and class I antiarrhythmic drugs (lidocaine, quinidine)--experimental studies in rabbit atrial myocardium.

UNLABELLED: Cholinergic agents exert no direct effect on the fast Na+ inward current but may influence the binding characteristic of class I antiarrhythmic drugs in atrial myocardium by shortening the action potential (AP) duration or by increasing the resting potential (RP). In order to examine such possible interactions we performed experiments using conventional intracellular microelectrodes on isolated preparations of rabbit atrial myocardium (Ke 2.7 mM, temperature 32 degrees C). At first the influence of the cholinergic agent carbachol (1 mg/l = 6.7 x 10(-6) M) on the RP and AP was examined at different stimulation rates (1.0, 2.5, and 3.3 Hz). Thereafter measurements were repeated under the influence of lidocaine (10 mg/l = 2.2 x 10(-5) M) or quinidine (5 mg/l = 2.2 x 10(-5) M) alone and in combination with carbachol (1 mg/l). RESULTS: (statistically significant differences, p less than 0.05): Carbachol increased the RP by about 10 mV and shortened the AP by about 60%. The maximal upstroke velocity of the AP (Vmax) was not significantly altered at 1.0 and 2.5 Hz, but increased under carbachol at 3.3 Hz. After addition of carbachol to the lidocaine-containing solution, Vmax increased to its control level at all stimulation rates. In experiments with quinidine, Vmax also increased after addition of carbachol but remained significantly below the control values. CONCLUSIONS: Carbachol effects on Vmax are most likely attributable to earlier recovery (caused by the shortening of the AP) and to faster recovery kinetics (due to hyperpolarization). The attenuation of the class I effect of lidocaine by carbachol can thus be considered mainly a consequence of the shortening of the inactivated state which results in a reduced affinity of lidocaine to its receptor and allows earlier dissociation of the drug. Minor binding of the drug due to hyperpolarization may play the major role in interactions between carbachol and quinidine.

Action Potentials↗

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Hemodynamic changes and renal plasma flow in early heart failure: implications for renin, aldosterone, norepinephrine, atrial natriuretic peptide and prostacyclin.

Vasoconstrictory and vasodilatory hormone systems may be important in the regulation of peripheral vascular resistance and renal hemodynamics in the early phase of heart failure. The activity of the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous activity, and, as possible counterregulating systems, the activity of prostacyclin and atrial natriuretic peptide (ANP) were studied in 6 conscious dogs during the first 4 days of congestive heart failure in relation to hemodynamic changes and renal plasma flow. Congestive heart failure was induced by rapid right ventricular pacing, which caused a considerable decrease of cardiac output (-38%; p less than 0.05), oxygen saturation of the mixed venous blood (-13%; p less than 0.05), and mean arterial pressure (-24 mm Hg; p less than 0.05) on the 4th day. Mean pulmonary arterial pressure and mean pulmonary capillary wedge pressure increased (+4 mm Hg; p less than 0.05 and +7 mm Hg, respectively; p less than 0.05). Renal plasma flow was slightly reduced (N.S.), renal vascular resistance did not change. Peripheral vascular resistance showed a significant increase only on the 1st day. Sympathetic nervous activity was stimulated (from 175 +/- 31 pg/ml to 391 +/- 100 pg/ml; p less than 0.05), while plasma renin concentration was significantly suppressed on the 4th day (from 3.3 +/- 0.4 ngAI/ml/h to 1.9 +/- 0.5 ngAI/ml/h; p less than 0.05), and plasma aldosterone levels were decreased (from 108 +/- 12 pg/ml to 76 +/- 12 pg/ml; p less than 0.05). ANP increased 3-fold (p less than 0.05) and 6-keto-prostaglandin F1 alpha increased in 4 out of 6 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

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Changes in myocardial substrate and energy metabolism by S-(4)-hydroxyphenylglycine and an N-(6)-derivative of adenosine.

In 15 mongrel open chest dogs oxidative myocardial carbohydrate utilization was stimulated by activation of pyruvatedehydrogenase with S-(4)-hydroxyphenylglycine (HPG) or by inhibition of lipolysis with N(6)-allyl-N(6)-cyclohexyladenosine (PAA). HPG and PAA shifted cardiac respiratory quotients (RQ) from 0.83 to 0.89 and 0.99, respectively. Oxygen extraction ratio of lactate was significantly increased by both interventions. Arterial nonesterified fatty acids (NEFA) concentration decreased significantly only by PAA. The oxygen saving potency of both interventions was quantified over a wide hemodynamic range by comparing the directly measured myocardial oxygen consumption (MVO2) with the myocardial energy requirements calculated from its hemodynamic determinants according to the Bretschneider formula during base conditions and beta-stimulation. Inhibition of peripheral lipolysis with PAA reduced MVO2 by 14%, enzyme activation with HPG by 8%. The results show that the efficiency of the myocardial energy supply can be influenced by manipulation of the oxidative substrate metabolism.

Adenosine↗

PubMedDate not supplied

Alpha-receptor constriction induced by atrial fibrillation during maximal coronary dilatation.

The mechanism of coronary vasoconstriction induced by atrial fibrillation during maximal coronary dilatation was studied in 19 chloralose-urethane anesthetized dogs. Maximal coronary dilatation was achieved by carbochromene (5 mg/kg i.v.) or dipyridamole (0.2 mg/kg i.v.). Left circumflex coronary blood flow was measured with an electromagnetic flowmeter. Atrial fibrillation was compared with rhythmic atrial pacing at similar heart rates (207 +/- 12 vs. 204 +/- 12 beats/min). During maximal coronary dilatation, coronary resistance was 0.38 +/- 0.05 mm Hg X min X 100 g/ml (RU) at sinus rhythm, 0.41 +/- 0.06 RU at atrial pacing, and 0.52 +/- 0.07 RU at atrial fibrillation, that was significantly (p less than 0.005) higher than during sinus rhythm and atrial pacing. Accordingly, coronary oxygen extraction was 14 +/- 1% at sinus rhythm, 17 +/- 1% at atrial pacing (p less than 0.005 vs. sinus rhythm) and 27 +/- 2% at atrial fibrillation (p less than 0.001 vs sinus rhythm and atrial pacing). Beta-adrenoceptor blockade with propranolol (1 mg/kg i.v.) did not prevent this coronary vasoconstrictive effect. Following alpha-blockade with phenoxybenzamine (10 mg/kg i.v.), however, coronary resistance was 0.52 +/- 0.08 RU during sinus rhythm, 0.54 +/- 0.10 RU during atrial pacing and 0.57 +/- 0.09 RU during atrial fibrillation. The data suggest coronary vasoconstriction induced by atrial fibrillation mediated by an alpha-adrenoceptor mechanism.

Animals↗

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Acute effect of calcium channel blockers on adriamycin exposed isolated adult cardiocytes.

When tested with isolated, calcium-resistant resting rat cardiocytes in an in vitro assay system, adriamycin exerted a dose-dependent cytotoxic effect which could easily be assessed by the ATP depletion of the heart cells and the loss of vitality as monitored by morphological changes (blebbing, spherical contraction). Apart from extremely high non pharmacological concentrations of verapamil and diltiazem, both calcium antagonists left the cardiocytes intact and without loss of internal ATP when given alone to the medium. Coincubation of adriamycin and verapamil or diltiazem did not increase adriamycin toxicity to the cardiocytes; instead a remarkable ATP preservation by verapamil could be demonstrated when both drugs (adriamycin and verapamil) were incubated simultaneously with the heart cells. This acute protective effect was limited in time and could no longer be detected after 9 hours. Diltiazem in coincubation experiments exerted neither a toxic nor an acute protective effect on adriamycin-exposed heart cells.

Adenosine Triphosphate↗

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Is the rat a suitable model for studying alcoholic cardiomyopathy? Hemodynamic studies at various stages of chronic alcohol ingestion.

Three groups of wistar rats with chronic alcohol consumption were studied: 10% ethanol for 6 months, 20% ethanol for 7 months, 20% ethanol for 12 months. In the intact heart in situ, left ventricular parameters of pressure, volume, and blood flow were recorded. On the average, body weight and heart weight of the alcohol-fed rats (A) were diminished by 10% as compared with controls (C). If end-diastolic volume is related to heart weight, no significant differences in the pressure-volume relations between C and A were obtained. There were no differences in the rate of pressure rise, nor in the end-systolic pressure-volume relations. According to these findings and the results of other authors, it is concluded that the rat is not very suitable for studying "alcoholic cardiomyopathy".

Animals↗

PubMedDate not supplied

Immunological parameters in patients with congestive cardiomyopathy.

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Antibodies↗

PubMedDate not supplied

Influence of acute alcohol intoxication on the left ventricular pressure-volume relations of the rat heart.

In 17 Wistar rats isovolumetric pressure-volume diagrams, the rate of pressure rise, and the resting tension curve were recorded prior to and during acute alcohol intoxication. Ethyl alcohol was infused intravenously; parameters were recorded at blood alcohol levels between 0.6% and 0.2%. The following results were obtained. 1. In agreement with other authors, even slight amounts of alcohol induced significant cardiodepression. 2. At high blood alcohol levels the isovolumetric pressure-volume relation is shifted to higher enddiastolic volumes and pressures. 3. The alcohol-induced cardiodepression is dose-dependent. There is a linear correlation between the maximum rate of pressure rise and the blood alcohol level.

Alcoholic Intoxication↗

PubMedDate not supplied

Influence of beta-adrenergic stimulation on the fast sodium current in the intact rat papillary muscle.

The loose-patch-clamp technique was used on intact cardiac papillary muscle of the rat to examine whether the fast sodium inward current (INa+) is influenced by the beta-adrenergic stimulant isoproterenol (ISO) or by 8-bromo-3',5'-cyclic adenosine monophosphate (8-Br-cAMP), respectively. The amplitude of INa+ evoked by test pulses of 5 ms to a transmembrane potential of 0 mV and its time to peak were analyzed. The availability of INa+ was tested with conditioning pulses of 2.5 s to potentials between -130 mV and -50 mV. The potential of half-maximal availability was slightly shifted to more negative values by 1 microM ISO (2.0 mV, n.s.), as well as by 50 microM 8-Br-cAMP (4.0 mV; p less than 0.05). The peak amplitude of INa+ elicited from strongly negative potentials was increased by ISO (18%, n.s.), while 8-Br-cAMP exerted no directional effect. Depolarizing conditioning pulses (-60 mV) decreased INa+ to 13.3% of the maximal attainable current under control conditions, while ISO decreased INa+ to 9.1% of control (p less than 0.1). Corresponding values under the influence of 8-Br-cAMP were 11.4% and 8.3% (p less than 0.05). Moreover, in the presence of ISO there was a significant shortening of the time to peak of INa+ (0.56 ms to 0.50 ms at -80 mV conditioning potential, p less than 0.05) which could not be detected in the presence of 8-Br-cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

PubMedDate not supplied

Vasopressin and renin in high output heart failure of rats: hemodynamic effects of elevated plasma hormone levels.

We studied the hemodynamic effects of vasopressin and the renin-angiotensin system in an animal model of high output heart failure in conscious rats (aorto-caval fistula). We found significantly elevated levels of plasma renin concentration (p less than 0.025), norepinephrine (p less than 0.02), and up to 4 to 5 times higher values of vasopressin (p less than 0.002) in the rats with heart failure as compared with control animals. In contrast to the control rats that had a normally functioning osmoreceptor system, we found an inverse relationship between plasma osmolality and arginine vasopressin in the rats with heart failure in association with edema. Using a specific antagonist of the pressor activity of vasopressin, we found no significant effect on heart rate, mean arterial pressure, cardiac output (thermodilution), and peripheral vascular resistance in the control animals and in the rats with aorto-caval fistula. Captopril resulted in a significant fall of mean arterial pressure in the rats with shunt (p less than 0.001). The coincidence of high values of vasopressin and, in a number of animals, low plasma osmolalities and edema suggests a role of vasopressin in the formation of edema and in the development of "dilutional hypo-osmolality."

Animals↗