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Biomedical subjects

D Bose

Publications and source records attributed to D Bose.

At least 55 records · Page 3Linked to original sources
PubMed1990

hemofiltration reverses left ventricular dysfunction during sepsis in dogs.

Depressed left ventricular (LV) contractility in sepsis has been ascribed to the presence of circulating cardiodepressant substance (filterable cardiodepressant factor in sepsis [FCS]); however, this finding is controversial. The authors hypothesized that if a decrease in LV contractility indeed occurred due to a circulating depressant substance, then removal of this substance by hemofiltration would reverse by dysfunction. In this study, LV mechanics were examined before and after hemofiltration in anesthetized dogs during continuous intravenous infusion of live Escherichia coli. Left ventricular anterior-posterior and apex-base dimensions were measured by subendocardial ultrasonic crystal transducers implanted 4 weeks before the experiments. Left ventricular contractility was determined from the end-systolic pressure-dimension relationship. The slope of this relationship (Emax) is an index of contractility. After 4 h of sepsis, Emax was reduced by one half. Hemofiltration resulted in a return of Emax to control values. The FCS activity in the plasma was also assessed by the percent reduction in isometric contraction of electrically stimulated, isolated right ventricular trabeculae obtained from nonseptic dogs. The FCS activity reached a peak 4 h after sepsis and was reduced after 2 h of hemofiltration. The results show that during experimental sepsis, a circulating substance of less than 30,000 d produces a decrease in LV contractility and that this LV dysfunction may be improved by hemofiltration.

Animals↗
PubMed1990

Positive inotropic effect of porcine left ventricular extract on canine ventricular muscle.

1. We previously isolated an extract from porcine left ventricle that possessed digitalis-like properties such as inhibition of cardiac and kidney Na+, K(+)-ATPase, displacement of [3H]-ouabain from its binding sites and cross reactivity with digoxin antibodies. The extract also had a positive inotropic effect on the guinea-pig heart. 2. In the present study the positive inotropic response of the extract was characterized in canine right ventricular trabeculae. Maximum inotropic response (501 +/- 20%) was produced by 300 microliters and the half maximal increase occurred with 125 microliters of the extract. 3. Ouabagenin produced aftercontractions in rapidly paced trabeculae. Equipotent and even greater amounts of the extract did not produce aftercontractions. 4. The extract increased the amplitude of the delayed component (P2) of biphasic contractions produced by replacing about 92-96% of the external Ca with Sr. A smaller increase in the size of the early component (P1) was also seen. 5. The extract decreased post-rest potentiation after rest for 30s and 2 min. After 8 min of rest, post-rest potentiation was converted to post-rest depression. 6. The extract (20 microliters) produced a decrease in the amplitude of the post-rest rapid cooling contracture (RCC) at all rest intervals. The steady state RCC, although greater than that in the control muscle, was increased to a lesser extent than the size of the steady state electrically driven contractions. 7. It is suggested that the extract from porcine left ventricle produces a positive inotropic response by increasing the trans-sarcolemmal influx of Ca. It also has additional effect(s) on the sarcoplasmic reticulum in that it may facilitate the loss of Ca from the sarcoplasmic reticulum and/or inhibit the uptake of Ca by the organelle.

Animals↗
PubMed1989

Cardiac glycoside-like structure and function of 5 beta,14 beta-pregnanes.

5 beta-Reduction and 14 beta-substitution convert the planar progesterone molecule to the cardiac glycoside configuration--A and D rings of the steroid moiety are bent toward the alpha-face relative to the B and C rings. Potency of the 5 beta,14 beta-derivative in a [3H]ouabain binding assay or its ability to inhibit the sodium pump in red blood cells is enhanced by 3 beta-hydroxylation, 20 beta-hydroxylation, and 3 beta-glycosidation. Synthesis of 14,20 beta-dihydroxy-3 beta-(beta-D-glucopyranosyloxy)- 5 beta,14 beta-pregnane from digitoxin is described. The glucoside is 1/20 as potent as ouabain and elicits prominent, sustained, positive inotropy in isolated cardiac muscle.

Animals↗
PubMed1989

Role of endothelium in hypoxic contraction of canine basilar artery.

1. Reversible contraction of canine basilar artery, produced by hypoxia, persisted after mechanical and chemical removal of the endothelium. The removal of endothelium was confirmed by scanning electron microscopy as well as by the abolition or reversal of the relaxant response to acetylcholine or arginine8-vasopressin. 2. Hydroquinone, believed to block selectively endothelium-mediated relaxation, also preferentially attenuated hypoxic contractions even in the absence of endothelium but did not reduce responses to 5-hydroxytryptamine (5-HT) or high external potassium. 3. Contractions induced by red blood cell haemolysate, which occur independently of the endothelium, were also selectively attenuated by hydroquinone. 4. Contractions caused by hypoxia were inhibited by pretreatment with adenosine or by its application after contraction had developed. 5. Hypoxic contraction in canine basilar artery may result partly from a direct effect on smooth muscle as well as through the endothelium. 6. Hydroquinone may have an additional locus of action in smooth muscle cells besides its well known effect on the endothelium.

Adenosine↗
PubMed1989

Effects of caffeine and ryanodine on depression of post-rest tension development produced by Bay K 8644 in canine ventricular muscle.

1. Post-rest inotropy in canine ventricular myocardium has proved a useful indicator of sarcoplasmic reticular calcium release. This phenomenon is converted to rest depression by the calcium channel activator (agonist), Bay K 8644 as well as other chemically diverse agents such as caffeine and ryanodine. 2. Rapid cooling contractures and post-rest contraction amplitude were used as independent measures of sarcoplasmic reticular calcium content and release. Simultaneous recordings of transmembrane action potentials and their accompanying contractions were obtained to determine the association between electrophysiological and mechanical events. The present study was designed to elucidate the mechanism by which Bay K 8644, caffeine and ryanodine alter force production after variable periods of rest. 3. Bay K 8644 (1 microM) increased steady state contraction in response to a constant train of stimulation, caused rest-depression after 2 and 8 min rest, prolonged action potential duration and increased action potential plateau amplitude. Augmented steady state tension was not accompanied by any change in time to peak tension or rapid cooling contracture amplitude. However, the post-rest rapid cooling contracture was greatly diminished compared to that observed prior to Bay K 8644 treatment. 4. Caffeine (3 and 5 mM) caused rest-depression with an increase in steady state contraction amplitude. Along with this there was a slight decrease in action potential duration and plateau amplitude and an increase in time to peak tension. The rapid cooling contractures were virtually abolished at all conditioning intervals. The effect of caffeine on twitch tension and cooling contracture is consistent with the ability of this compound to inhibit calcium sequestration by the sarcoplasmic reticulum. 5. A combination of Bay K 8644 and caffeine caused significantly less rest-depression than that seen with Bay K 8644 alone. The augmented twitch tension was accompanied by a long time to peak tension and action potential duration. However, there was no increase in the amplitude of the rapid cooling contracture, either after a regular train of stimulation or after rest, compared to that seen after Bay K 8644. 6. Ryanodine (10 nM), produced rest-depression, reduced steady state twitch tension and augmented the rest-depression produced by Bay K 8644. The steady state rapid cooling contracture remained unchanged when both agents were present simultaneously, while the post-rest rapid cooling contracture was significantly depressed compared to that observed with Bay K 8644 alone. 7. Bay K 8644 and ryanodine appear to have similar actions with respect to promoting diastolic loss of calcium from the sarcoplasmic reticulum. Although caffeine also decreases post-rest potentiation, it antagonizes rest-depression caused by Bay K 8644. The data from these experiments suggest that this reversal is a result of depressed intracellular calcium buffering and enhanced myofilament sensitivity produced by caffeine in the presence of increased transmembrane calcium influx promoted by Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Ouabain prevents loss of autoregulation in rat pial arterioles caused by reoxygenation after a brief hypoxic episode.

Pial arteriolar diameter changes inversely with changes in systemic arterial blood pressure. Such changes are consistent with autoregulatory functions. These responses are reduced by a brief period of hypoxia followed by reoxygenation. By using an open cranial window preparation we assessed the changes in pial arteriolar diameters during blood pressure changes in rats induced by hemorrhage and reinfusion of blood, before and after a brief period of hypoxia. The slopes of the changes in pial arteriolar diameter as a function of mean arterial blood pressure were -0.47 +/- 0.26 micron/mmHg (mean +/- SD; 1 mmHg = 133.3 Pa) before hypoxia and -0.11 +/- 0.23 micron/mmHg after hypoxia in the untreated rats. In ouabain-treated rats, corresponding slopes were -0.42 +/- 0.24 and -0.46 +/- 0.22 micron/mmHg. The observed protective effects of ouabain might be a blockade of the Na-K pump in the sarcolemma of the vascular smooth muscle.

Animals↗
PubMed1989

Analysis of the effects of (-) and (+) isomers of the 1,4-dihydropyridine calcium channel agonist BAY k 8644 on postrest potentiation in the canine ventricular muscle.

Contraction of canine ventricular trabeculae were recorded stimulation at a frequency of 0.5 Hz and after rest periods of 2 and 8 min to analyze the effect of the Ca channel agonist BAY k 8644, on sarcoplasmic reticular function. Short periods of rest interposed between steady trains of stimuli caused a potentiation of the postrest beat. This is believed to be due to the mobilization of activator Ca from the sarcoplasmic reticulum (SR). Racemic BAY k 8644 and its Ca channel agonist enantiomer, (-) BAY k 8644, both produced an increase in contraction in response to a steady train of stimuli but converted rest potentiation into rest depression. This has been interpreted as increased loss of Ca from the SR during diastole. Addition of Ca channel antagonists, (+) BAY k 8644, nitrendipine, or nifedipine, to reverse the agonistic effect of (-) and racemic BAY k 8644 on the Ca channel did not convert the rest depression into rest potentiation. In the presence of stimuli but converted rest potentiation into rest depression. This has been interpreted as increased loss of Ca from the SR during diastole.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Inhibition of rest potentiation in canine ventricular muscle by BAY K 8644: comparison with caffeine.

Rest potentiation, believed to be due to increased utilization of sarcoplasmic reticular calcium, was converted to rest depression by BAY K 8644 (1 microM). Plateau height and duration of the postrest beat were enhanced by BAY K 8644, suggesting an enhancement of extracellular calcium entry. Caffeine (3 mM) also produced depression at all rest intervals, although to a lesser extent than BAY K 8644. Compared with BAY K 8644, treatment with caffeine resulted in an elevation of plateau amplitude and a shortening of action potential duration. Action potential configuration changes induced by rest were unaltered by caffeine despite reduction in rest potentiation. Caffeine-induced rest depression was associated with an increase in the time to peak tension. This was not observed with BAY K 8644. Treatment with both caffeine (3 mM) and BAY K 8644 (1 microM) greatly prolonged time to peak tension. Action potential duration and plateau height were either maintained or increased. Less rest depression was observed with the combination than with either agent alone. These results suggest that 1) BAY K 8644 and caffeine inhibit rest potentiation by different mechanisms, and 2) caffeine-induced inhibition of calcium uptake by the sarcoplasmic reticulum may enhance the effect of BAY K 8644-induced increase in calcium influx on the contractile apparatus.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Possible inhibition of canine ventricular sarcoplasmic reticulum by BAY K 8644.

The calcium-channel agonist-antagonist racemic mixture of BAY K 8644 as well as the pure calcium-channel agonist enantiomer, converted rest potentiation in canine ventricular muscle to rest depression. The depressed postrest beats had increased action potential plateau heights and durations, suggesting that extracellular calcium entry was enhanced. BAY K 8644 did not alter the time to peak tension of either steady-state or postrest beats. Although BAY K 8644 slightly increased the amplitude of rapid-cooling contractures (RCC) immediately after an electrically evoked steady-state contraction (RCCss), the RCC amplitude rapidly decreased with increasing durations of rest. These results suggest that increased calcium influx because of BAY K 8644 increases the pool of releasable calcium during steady-state stimulation. However, they also indicate that BAY K 8644 causes acceleration of diastolic loss of calcium from the sarcoplasmic reticulum (SR). Scattered light intensity fluctuation measurements showed that the negative inotropic effect of BAY K 8644 on postrest contraction was not caused by calcium overloading of the SR, since BAY K 8644 reduced asynchronous myofilament motion. A negative relationship found between extracellular calcium and BAY K 8644-induced postrest depression also rules out the possibility that the latter effect is caused by intracellular calcium overload. BAY K 8644 seems to accelerate the loss of calcium from the SR during diastole by a pathway that does not appear to pass through the myofilaments.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Analysis of the interval-force relationship in rat and canine ventricular myocardium.

The mechanism of the negative force staircase in thin rat ventricular trabeculae was investigated and compared with the positive force staircase in dog ventricular muscles of comparable diameter. Increasing stimulus frequency from 0.2 to 0.5 and 1 Hz resulted in a stepwise reduction of twitch amplitude that was demonstrated in both 1.25 and 2.5 mM external calcium concentration ([Ca]o). The negative staircase was associated with no change in the amplitude of postrest contraction or rapid-cooling contracture at either [Ca]o investigated. Hence, neither decreased loading nor overloading of the rat sarcoplasmic reticulum with calcium during the steady state can be invoked as a likely explanation for the negative staircase. The results are consistent with a frequency-dependent increase in the refractoriness of the sarcoplasmic reticular calcium release process or a decrease in the amount of trigger for calcium release, assuming that the amount of calcium present in the release pool is constant from one frequency to the next. In contrast to the rat, canine ventricular muscle exhibited a positive force staircase, the slope of which depended on [Ca]o, as well as a frequency-dependent increase in postrest contraction and rapid-cooling contracture. Data obtained from this series of experiments suggests that increased filling of the release pool within the sarcoplasmic reticulum with calcium underlies the inotropic effect of high-frequency stimulation in canine ventricular muscle.

Animals↗
PubMed1988

14 beta-Hydroxyprogesterone binds to the digitalis receptor, inhibits the sodium pump and enhances cardiac contractility.

1. Certain derivatives of progesterone are potent inhibitors of high affinity, specific binding of 3H-cardiac glycosides. The steroids interact at the cardiac glycoside site on Na,K-ATPase and inhibit the enzyme (the sodium pump) in cardiac and other tissues. However, the active congeners identified previously have been, unlike the cardiac glycosides, predominantly cardiodepressant. 2. Because a 14 beta-hydroxy substituent is an important determinant of activity of the cardiotonic cardiac glycosides, we synthesized 14 beta-hydroxyprogesterone. This derivative has about one-tenth the potency of the aglycone, ouabagenin, in a [3H]-ouabain binding assay. 3. Like ouabagenin, but in contrast to the cardiodepressant congeners of progesterone, 14 beta-hydroxyprogesterone consistently elicited positive inotropy in isolated cardiac muscle and enhanced both the magnitude and frequency of fluctuations in scattered light (an index of oscillatory intracellular release of calcium). 4. Thus, at least one hydroxylated derivative (and putative endogenous metabolite) of progesterone, mimics the cardiac effects of cardiac glycosides including enhanced contractility.

Adult↗
PubMed1988

Impairment of Ca release from mammalian ventricular sarcoplasmic reticulum by the calcium channel agonist Bay K 8644.

Positive inotropic concentration of the Ca-channel agonist, Bay K 8644, depressed contraction of canine right ventricular trabecula immediately after a rest period of 8 min, without decreasing action potential plateau amplitude. In contrast, high external Ca and ouabagenin caused only a slight decrease in post-rest contraction. Bay K 8644-induced post-rest depression was inversely related to the extracellular Ca concentration. Hence it could not be due to cellular Ca overload. Since post-rest potentiation is due to increased contribution of Ca from the sarcoplasmic reticulum, these results suggest that Bay K 8644 decrease the amount of releasable Ca from this structure during rest.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Control of interval-force relation in canine ventricular myocardium studied with ryanodine.

1. The mechanism of post-extrasystolic, rest and frequency potentiation was studied in canine isolated ventricular muscle. 2. Ryanodine, which impairs Ca availability from the sarcoplasmic reticulum (SR), reduced the amplitude of the extrasystole less than that of the steady state contraction. Ryanodine also inhibited post-extrasystolic potentiation and converted rest-potentiation into rest depression. Rest-potentiation was blocked preferentially by ryanodine compared to post-extrasystolic potentiation. An increase in the contribution of extracellular Ca to the extrasystolic contraction could not entirely account for the post-extrasystolic potentiation. 3. Prolonged rest, by itself, also caused depression of the first post-rest contraction. During rest-potentiation, SR Ca seemed to play a greater role in contraction than transmembrane Ca influx. However, the ability of the 'release pool' of Ca in the SR to be reprimed after a contraction was reduced. This was seen as a decrease in post-extrasystolic potentiation elicited immediately after rest. 4. A decrease in stimulus interval was associated with a transient decrease in contraction amplitude followed by an increase. An abrupt increase in stimulus interval had the opposite effect. Ryanodine blocked the initial transient changes and accelerated the delayed changes. These results suggest that the transient changes in contraction after sudden changes in drive interval are dependent on the SR. 5. Transmembrane Ca entry and the rate of recovery of the Ca release process (repriming) in the SR after a contraction seem to be interval-dependent. The data also indicate that different mechanisms are involved in post-extrasystolic and rest-potentiation. 6. The results are consistent with a model which proposes 'recirculation' of activator Ca within the SR after a contraction or of the presence of an appreciable amount of inactivation of the SR Ca release process during normal stimulation. An increased pool of releasable Ca due to longer recirculation time or a time-dependent decay in the level of inactivation of Ca release from the SR may give rise to rest-potentiation.

Alkaloids↗
PubMed1988

Scattered light intensity fluctuation in the canine ventricular myocardium: correlation with inotropic drug effect.

Scattered light intensity fluctuation (SLIF) of coherent light by a strip of ventricular muscle during diastole is believed to be due to asynchronous cellular motion within the myocyte as a result of spontaneous release of Ca from the sacoplamic reticulum. Previous studies have shown a correlation between inotropic agents, such as ouabain and elevated extracellular Ca or decreased extracellular Na, and SLIF. The purpose of this study was to see if this correlation could be extended to other inotropic agents. The digitalis genin, ouabagenin, produces inotropy by increasing intracellular free Ca. In toxic concentrations the drug produces abnormal aftercontractions by spontaneous Ca release from the sarcoplasmic reticulum. On the other hand, the Ca channel agonist BAY k 8644 is also positively inotropic, but its effect is associated with a decrease in Ca release from the sarcoplasmic reticulum, manifested by conversion of "rest potentiation" to "rest depression." The effects of these inotropic agents on the power spectra of SLIF were dissimilar. Both frequency and amplitude of SLIF were increased after ouabagenin (1 microM), but these changes were most marked after the onset of toxicity, at which time contractility was decreased, rather than during the positive inotropic response. In contrast, BAY k 8644 (1 microM) decreased SLIF at all levels of inotropic response. The beta-adrenoceptor stimulant drug, dobutamine, and the adenylate cyclase activator, forskolin, produced minimal increase in SLIF at inotropic concentrations but caused a large increase in SLIF only after the onset of toxicity. These results suggest that SLIF is a better indicator of intracellular Ca overload and toxic oscillatory contractions in the presence of an inotrope and not of increased inotropy, per se.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Digitalis-like pregnanes. Cardiac and renal effects of a glycoside of 14 beta-hydroxyprogesterone.

The synthesis of the glucoside, 3 beta-[(beta-D-glucopyranosyl)oxy]-14-hydroxy-14 beta-pregn-4-en-20-one, a 14 beta-hydroxyprogesterone glucoside (14 beta-OHP-glu), is described. This compound has an IC50 of 1 microM in a [3H]ouabain binding assay, and is about 10 times more potent than the aglycone. Like 14 beta-hydroxyprogesterone, the glucoside enhances contractility of isolated cardiac muscle. 14 beta-OHP-glu or ouabain, when infused at comparable doses into the renal artery of the anesthetized rat, markedly increases urine volume. Whereas ouabain significantly enhances urinary potassium excretion with little or no effect on sodium excretion, 14 beta-OHP-glu promotes a marked natriuresis with no significant effect on potassium excretion.

Animals↗
PubMed1988

Effect of subarachnoid hemorrhage on intracranial pulse waves in cats.

The influence of vasoconstrictors of intracranial arteries on the amplitude and configuration of the intracranial pulse wave (ICPW) was investigated. Continuous pressure recordings from the descending aorta (systemic arterial pressure) and the third cerebral ventricle (intracranial pressure) were obtained from anesthetized cats. Computerized analysis of the configuration, amplitude, and frequency spectrum of ventricular wave (ICPW) and aortic pulse wave (SAPW) was performed. Artificial cerebrospinal fluid (CSF), blood, or 5-hydroxytryptamine (5-HT) was injected intracisternally. In 24 control cats, 2 ml artificial CSF was injected into the cisterna magna. This produced a significant increase in amplitude of the ICPW but no change in the SAPW. Ten animals received 14 intracisternal injections of 2 ml autologous blood which caused narrowing of the amplitude of the ICPW as well as of all its components (P1, P2, and P3), with no significant change in the SAPW's. Eight animals were also subjected to cisternal injection of 2 ml of a 10(-4)-M solution of 5-HT, resulting in findings similar to those produced by autologous blood. Frequency spectrum of the intracranial and aortic pulse waves showed a high degree of correlation between wave amplitudes and height of the fundamental wave in the FFT record. These results suggest that the cerebral vasospasm that follows cisternal injections of blood and 5-HT in cats can be diagnosed by analysis of the ICPW. This method may allow early diagnosis and continuous monitoring of cerebral vasospasm in humans.

Animals↗