PubMed Health⌕ Search

Biomedical subjects

A M Shah

Publications and source records attributed to A M Shah.

At least 19 recordsLinked to original sources
PubMed1992

Endothelial modulation of myocardial contraction: mechanisms and potential relevance in cardiac disease.

Recent studies in isolated cardiac preparations and the intact heart demonstrate that the endocardial and coronary vascular endothelium modulate myocardial contractile behaviour and cardiac pump function in a novel manner, mainly by influencing the duration of contraction and the onset of relaxation but without major effect on early systolic contractile characteristics. These effects are mediated by the release of at least two diffusible substances from endothelial cells: a) endothelium-derived relaxing factor (EDRF) which shortens contractile duration by elevating myocardial cyclic GMP, and b) a novel substance, provisionally named "endocardin", which prolongs contractile duration. Under physiological conditions these endothelial influences may be particularly important for relaxation and early diastolic filling events in the heart. It is possible that they could influence myocardial growth, interact with other cardiac hormones, and via EDRF inhibit platelet adhesion to endothelial surfaces. The release of the endothelial factors is regulated by stimuli such as circulating neurohumoral substances, increased flow, products of platelet aggregation, and endogenous peptides stored in endothelial cells. Although experimental evidence is still limited, it seems likely that cardiac endothelium may play an important role in the pathophysiology of cardiac disease, e.g. overload-induced hypertrophy. The endothelium could a) influence the development of phenotype change by modulating and mediating transduction of extrinsic signals, b) contribute to contractile and other abnormalities (especially "diastolic" dysfunction) because of loss or impairment of its normal function, and c) be uniquely amenable to therapeutically useful pharmacological manipulation.

Animals↗
PubMed1992

The influence of endocardial endothelium on myocardial contraction.

A novel unidentified agent, provisionally named 'endocardin', has been shown to be released from endocardial endothelium. Endocardin has a unique prolonging effect on myocardial contraction. In contrast, endothelium-derived relaxing factor released from endocardial endothelium has the opposite effect of abbreviating contraction. Jerry Smith and colleagues discuss the mechanisms of action of these agents and their possible physiology and pathophysiology.

Animals↗
PubMed1992

Action potential duration and endocardial modulation of myocardial contraction in the ferret.

OBJECTIVE: Endocardial endothelium releases substances which modulate myocardial contraction. Selective endocardial removal abbreviates contraction by removing a contraction prolonging substance "endocardin". The aim of the study was to investigate whether changes in action potential duration underlie these contractile effects. METHODS: The contractile effects of shortening the action potential were first characterised, using a potassium channel "opener" cromakalim (3 microM). Transmembrane action potentials were then recorded in isolated ferret papillary muscles before and after endocardial removal. RESULTS: Cromakalim-induced action potential abbreviation reduced contractile twitch duration. Endocardial removal itself however did not alter action potential duration. CONCLUSIONS: Endocardial modulation of cardiac contraction does not involve changes in action potential duration.

Action Potentials↗
PubMed1992

Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret.

The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Effects of 8-bromo-cyclic GMP on contraction and on inotropic response of ferret cardiac muscle.

The effects of guanosine 3':5'-cyclic monophosphate (cGMP) on cardiac contraction are not established. Using isolated electrically-stimulated ferret papillary muscle at 29 degrees C, 2.0 mM calcium we investigated the effects of 8-Bromo-cGMP on (a) basal contraction for comparison with the effects of reduction in extracellular calcium or of reduction in resting muscle length; (b) contraction of preparations stimulated by isoprenaline, the dihydropyridine calcium agonist Bay K8644 or post-extrasystolic potentiation. 8-Bromo-cGMP (0.1 mM) induced a small significant reduction in isometric twitch tension (TT) (7%), isotonic shortening (PS) (6%) and in twitch duration, but had no effect on maximum unloaded shortening velocity (Vmax) or rate of tension development (+dT/dt). Reduction in muscle length induced a similar immediate effect on contraction. Reduction of extracellular calcium (2.0 mM to 1.25 mM) reduced TT by 24% and PS by 14% as well as Vmax (19%) and +dT/dt (29%), but did not alter twitch duration. Bay K8644 (0.01 to 10 microM) produced increases in TT, +dT/dt, PS and twitch duration each of which was significantly reduced in the presence of 8-Bromo-cGMP (0.1 mM). 8-Bromo-cGMP had no effect on the responses to isoprenaline 1 nM to 100 microM--which increased TT, +dT/dt and PS but markedly reduced twitch duration--nor on post-extrasystolic potentiation which increased TT and +dT/dt but slightly reduced twitch duration. These results show that 8-Bromo-cGMP induces changes similar to the immediate effects of reduction in resting muscle length, and reduces the positive inotropic effects of Bay K8644 but not those of isoprenaline or post-extrasystolic potentiation.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Factors released from endocardium of the ferret and pig modulate myocardial contraction.

1. In isolated heart muscle preparations, selective removal of the endocardium results in a characteristic and unusual negative inotropic effect. Possible mechanisms for this effect were investigated in this study. 2. In endocardium-intact preparations of ferret papillary muscle, 8-bromo-cyclic GMP, sodium nitroprusside, atrial natriuretic peptide (ANP) and substance P each induced changes in contractile behaviour similar to selective endocardial removal, and each significantly elevated myocardial cyclic GMP levels. Substance P failed to elevate myocardial cyclic GMP levels following removal of endocardium or in the presence of haemoglobin, suggesting that it may act by releasing endothelium-derived relaxing factor (EDRF) from endocardium. However, there was no change in myocardial cyclic GMP levels following endocardium removal alone. 3. In cascade bioassay experiments, it was confirmed that porcine cultured endocardial cells released an unstable humoral agent whose effects on an endothelium-denuded pig coronary artery were indistinguishable from EDRF. 4. The negative inotropic effects of endocardium removal were reversed in bioassay experiments where an endocardium-denuded papillary muscle was exposed to the effluent from a column of porcine cultured endocardial cells on microcarrier beads. This demonstrates for the first time the release of a 'contraction prolonging factor' from endocardium, the tonic release of which would explain the negative inotropic effect of endocardium removal. 5. It is concluded that elevation of ferret papillary muscle cyclic GMP (as for example with EDRF) produces changes in contractile performance similar to those induced by endocardium removal. We also demonstrate that superfused porcine cultured endocardial cells release a humoral agent (provisionally named 'endocardin') which causes reversal of the changes in mechanical properties seen after endocardial removal.

Animals↗
PubMed1990

Eosinophils from hypereosinophilic patients damage endocardium of isolated feline heart muscle preparations.

Persistent eosinophilia in humans is often associated with endocardial damage to the heart, but a causal relation has not been established. We investigated the effect of eosinophils and eosinophil supernatants obtained from eight hypereosinophilic patients on the contractile performance and endocardial morphology of isolated, electrically stimulated cat papillary muscle preparations (n = 16). All these eosinophil suspensions contained high proportions of "hypodense" or "activated" cells. Eosinophils (5-15 x 10(6) ml organ bath) or eosinophil culture supernatants (prepared by overnight incubation at 37 degrees C) when added to papillary muscles produced acute changes in contractile behavior of these muscles identical to the previously reported effects of selective endocardial damage: a reduction in time to peak isometric twitch tension causing a reduction in peak isometric tension but with no significant reduction in rate of tension development or in maximum unloaded shortening velocity. All of these muscle preparations showed severely damaged endocardium at scanning electron microscopy. Addition of eosinophils from hypereosinophilic patients to muscles with selectively damaged endocardium (by previous transient [1-second] exposure to 1% Triton X-100) produced no further change in contractile performance. No significant change in contractile performance or endocardial morphology of papillary muscles (n = 16) was observed after addition of eosinophils (7.5-10 x 10(6] or neutrophils (8-15 x 10(6] from normal subjects or of cell-free culture medium. Thus, activated human eosinophils produce specific morphological and functional changes suggestive of specific damage to endocardium of isolated feline cardiac muscle.

Adult↗
PubMed1990

Does endocardium modulate myocardial contractile performance?

It is now clear that the endocardium releases at least two agents which exert opposing effects on myocardial contraction. One appears to be endothelium-derived relaxing factor (EDRF), as in vascular endothelium, but the identity of the other is unknown. The mechanism by which these agents exert their characteristic but opposing effects on the duration of contraction likewise remains unknown. It is unlike that of other inotropic interventions and merits further investigation. Alterations in the time of onset of relaxation have important implications for diastolic filling.

Animals↗
PubMed1989

Inotropic effects of endothelin in ferret ventricular myocardium.

The characteristics of the inotropic response to endothelin were studied in isolated ferret papillary muscle preparations. Endothelin (0.1-10 nM) induced concentration-dependent positive inotropic effects. At 10 nM, isometric tension increased by 17%, maximum rate of tension development by 18%, maximum velocity of unloaded shortening by 23% and peak isotonic shortening by 11%. Time to peak isometric tension and half isometric relaxation time were unaltered by endothelin. This pattern of change is similar to that of elevating extracellular calcium concentration.

Animals↗
PubMed1989

Endocardium modulates myocardial inotropic response to 5-hydroxytryptamine.

The endocardium modulates contractile performance of subjacent myocardium in isolated heart muscle. We investigated the effects of 5-hydroxytryptamine (5-HT, 0.01-30 microM) on isolated cat papillary muscles with or without intact endocardium (+E or -E, respectively). Selective endocardial damage by 1-s immersion in 1% Triton X-100 caused reduction in half-isometric relaxation time (RT1/2) and isometric twitch tension (TT), but not maximum unloaded shortening velocity (Vmax). 5-HT caused reduction in RT1/2 in endocardium-intact but an increase in endocardium-damaged preparations (at 30 microM: -12.1 +/- 1.8%, +E; +5.2 +/- 1.5%, -E). Mean percent increases in TT were greater in endocardium-damaged muscles (at 30 microM: 37.3 +/- 8.6%, +E; 107.3 +/- 19.5%, -E). In the presence of ketanserin (1 microM), 5-HT reduced RT1/2 in endocardium-intact (at 30 microM: -11.9 +/- 1.3%) but not endocardium-damaged muscles (except slightly at 30 microM) and increased TT at 30 microM by 28.7 +/- 4.9% (+E) and 48.9 +/- 15.6% (-E). In the presence of propranolol (1 microM), 5-HT increased RT1/2 (+E and -E) while increasing TT by 23.3 +/- 7.8% (+E) and 43.5 +/- 2.5% (-E). Endocardium did not influence changes in Vmax. Ketanserin (1 microM), but not propranolol (1 microM), markedly diminished endocardial damage induced by 5-HT (greater than or equal to 10 microM). These results suggest a 5-HT-induced endocardium-mediated "inhibitory" effect (causing earlier isometric relaxation) that is not blocked by ketanserin.

Animals↗
PubMed1989

Myocardial inotropic responses to aggregating platelets and modulation by the endocardium.

Ventricular mural thrombi complicate many cardiac diseases. The endocardial endothelium can modulate the mechanical performance of subjacent myocardium and mediate responses to certain physiopharmacologic agents. We studied the effects of aggregating platelets on the contractile performance of isolated cardiac muscle. The role of the endocardium was investigated by selectively damaging it by very brief (1 second) exposure to 1% Triton X-100 in some muscle preparations before experiments. Cat papillary muscles (n = 54) were attached to an electromagnetic length-tension transducer in organ baths containing Krebs-Ringer solution (1.25 mM Ca2+, 35 degrees C), and stimulated electrically at 0.2 Hz. Homologous washed platelets (final concentration 3 x 10(11)/l) aggregated spontaneously on addition to baths. Mechanical performance increased significantly more in muscles with damaged endocardium than in intact muscles (p less than 0.05); total peak isometric twitch tension increased by 31.8 +/- 7.8% (with damaged endocardium) and 11.8 +/- 2.6% (with intact endocardium), and peak isotonic twitch shortening increased by 36.7 +/- 7.8% (with damaged endocardium) and 9.6 +/- 2.0% (with intact endocardium). Increases in maximum velocity of unloaded shortening were similar in both muscle groups. Time to half isometric twitch tension decline decreased in intact muscles (3.6 +/- 1.0%) but increased in Triton-treated muscles (2.5 +/- 1.3%, p = 0.003 for difference between groups). The inotropic response to platelets in muscles with intact endocardium was unaltered by pretreatment of muscles with indomethacin (10 microM) or by stimulation of platelet aggregation with thrombin (0.1 unit/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗