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Biomedical subjects

M Shahid

Publications and source records attributed to M Shahid.

At least 55 records · Page 3Linked to original sources
PubMed1989

The inotropic effect of 4-aminopyridine and pH changes in rabbit papillary muscle.

The effects of 4-aminopyridine (4AP), and pH changes have been examined on tension responses and cyclic nucleotide levels in rabbit isolated right ventricular papillary muscles. 4AP augmented papillary muscle contractions in a concentration-dependent manner. However, this positive inotropic action was largely due to an increase in extracellular pH produced by 4AP, rather than an intrinsic activity of the drug. Increases in extracellular pH (from 5 to 9) produced graded and reproducible increases in contractile force which were not blocked by propranolol (1 x 10(-7) M) but were inhibited by verapamil in a concentration-dependent manner. The positive inotropic effects of Ca2+ were enhanced and depressed by alkaline and acidic pH, respectively. Neither 4AP nor alkaline pH significantly changed cyclic AMP concentration in rabbit papillary muscles. The cyclic GMP content, however, was increased by 4AP only and this effect was blocked by atropine. The results suggest that the positive inotropic effect associated with a rise in pH from neutrality may be due to facilitation of translocation of membrane Ca2+ and/or to increase the release of Ca2+ from sources within the cell. They also illustrate that a major component of the inotropic effect of 4AP is a result of an increase in extracellular pH.

4-Aminopyridine↗
PubMed1988

Valve surgery in acute rheumatic heart disease. One- to four-year follow-up.

Six patients with acute rheumatic carditis and intractable left ventricular failure, all in class 4 NYHA classification, underwent successful valve surgery combined with medical therapy. Two-dimensional echocardiography and Doppler studies showed all of them to have left ventricular dilatation, with good systolic function, together with severe mitral regurgitation; two patients also had severe aortic regurgitation. Over a mean follow-up period of two years, no mortality was recorded, and all six patients were in NYHA class 1-2. We conclude that valve replacement is not contraindicated in acute rheumatic carditis and may be preferable to repair.

Acute Disease↗
PubMed1987

Effects of forskolin on contractile responses and protein phosphorylation in the isolated perfused rat heart.

Continuous perfusion of rat hearts with concentrations of forskolin between 0.1 and 12 microM resulted in transient increases in tension after 45 s, followed by a return to the control value after 5 min. In contrast, the content of cyclic AMP increased linearly with time over this period, reaching values up to 35 times control after 5 min. Increases in contractile force, intracellular cyclic AMP concentration and the proportion of phosphorylase in the a form were dependent on the concentration of forskolin when measured 45 s and 120 s after initiation of perfusion. In hearts perfused for 45 s with various concentrations of forskolin, the measured cyclic AMP-dependent protein kinase activity ratio and phosphorylase a content for a given measured intracellular cyclic AMP concentration were both much less than the corresponding values in hearts perfused for 30 s with various concentrations of isoprenaline. The phosphorylation of the contractile proteins troponin-I and C-protein also showed a concentration-dependent increase in hearts perfused with forskolin. There was a strong correlation between the cyclic AMP-dependent protein kinase activity ratios and the phosphorylation of the contractile proteins under all perfusion conditions. These results suggest that cyclic AMP is compartmented in perfused rat heart, and that much of the cyclic AMP produced in response to forskolin is unavailable to activate cyclic AMP-dependent protein kinase.

Animals↗
PubMed1985

The relationship between coronary artery occlusion-induced arrhythmias and myocardial cyclic nucleotide levels in the anaesthetized rat.

The aims of this study were to determine whether a relationship exists between the occurrence of coronary artery occlusion-induced arrhythmias in the anaesthetized rat and the levels of cyclic AMP and cyclic GMP in both normal and ischaemic myocardium, and to assess whether such arrhythmias were modified by pretreatment with the phosphodiesterase inhibitors, quazodine and isobutyl methylxanthine (IBMX), or with the butyryl derivatives of cyclic AMP and cyclic GMP. At 5 min after coronary artery ligation (when only a few arrhythmias had occurred) both cyclic AMP and cyclic GMP levels were elevated in normal myocardium whereas in ischaemic tissue only cyclic AMP was raised. As the peak of the arrhythmic activity and after cessation of the arrhythmias, i.e. at 10 and 30 min post-ligation respectively, levels of both nucleotides had fallen in ischaemic although not in normal tissue. The severity of these occlusion-induced arrhythmias was exacerbated by pretreatment intravenously with quazodine, IBMX, dibutyryl cyclic AMP and dibutyryl cyclic GMP. Pretreatment with IBMX was also shown to elevate significantly both cyclic AMP and cyclic GMP content of left ventricular tissue before occlusion. None of the drug pretreatments markedly affected mean arterial blood pressure but heart rate was significantly increased following quazodine and IBMX administration. We conclude that in the pentobarbitone-anaesthetized rat the occurrence of occlusion-induced arrhythmias was not accompanied by a rise in cyclic nucleotide content of the ischaemic myocardium but agents which may elevate either myocardial cyclic AMP or cyclic GMP levels exacerbate such arrhythmias.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Cyclic nucleotides and contractility of isolated soleus muscle.

The effects of isoprenaline, terbutaline and forskolin were examined on cyclic nucleotide concentrations and contractile responses in guinea-pig isolated soleus muscles. Isoprenaline and terbutaline induced rapid, concentration-related reductions in the tension and degree of fusion of subtetanic contractions of the soleus muscle. These changes were associated with increases (about 2 fold) in the levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the muscle cells. Propranolol competitively inhibited these responses. Forskolin failed to elicit a sympathomimetic response in the soleus muscles despite increasing (by about 20 fold) the intracellular concentration of cyclic AMP. Forskolin also failed to potentiate the effects induced by isoprenaline. The levels of cyclic GMP in the soleus were increased by isoprenaline (about 1.5 fold) and forskolin (about 2.5 fold). Terbutaline was without effect on cyclic GMP levels. These data suggest either that cyclic AMP is not involved as the mediator underlying beta-adrenoceptor-induced changes in contractility of slow contracting skeletal muscles or that forskolin does not stimulate the particular adenylate cyclase that leads to appropriate increases in cyclic AMP in those functional compartments associated with modulation of intracellular Ca2+ movements. Cyclic GMP is not involved in modifying changes in contractility of the soleus muscle.

Animals↗
PubMed1984

Forskolin, cyclic nucleotides and positive inotropism in isolated papillary muscles of the rabbit.

The effects of forskolin, isoprenaline, sodium nitroprusside and the frequency of stimulation were examined on cyclic nucleotide levels and tension responses in rabbit isolated right ventricular papillary muscles. Increasing the frequency of stimulation from 0.01 Hz to 1.6 Hz induced positive inotropic responses that were not obviously related to alterations in the level of either cyclic AMP or cyclic GMP. Isoprenaline induced rapid, concentration-related positive inotropic responses that were associated with increases in the levels of both cyclic AMP and cyclic GMP. There existed good correlations between the increases in tension and the concentrations of both cyclic nucleotides measured in the tissues. Forskolin induced concentration-related positive inotropic responses that were slow to develop. These responses were accompanied by concentration-related increases in the levels of cyclic AMP but not cyclic GMP. The tension responses correlated well with the levels of cyclic AMP measured. The cyclic AMP levels produced by forskolin were some 8 fold higher than those induced by isoprenaline for similar increases in tension. Sodium nitroprusside was without inotropic effect either positive or negative; it nevertheless elevated cyclic GMP levels whilst slightly reducing cyclic AMP levels. These data show that the ratio of cyclic AMP to cyclic GMP does not correlate well with changes in mammalian cardiac contractility. The data further suggest that whilst the intracellular concentration of cyclic AMP in rabbit ventricular myocardium may be an important determinant of positive inotropism, the relationship between the two parameters is more complex than simple proportionality between the tension generated and the amount of cyclic AMP measured within the cells.

Animals↗
PubMed1977

Diagnostic evaluation of hypertension: pilot study in a hypertension clinic.

Two hundred and eighty-two (282) patients suffering from hypertension were evaluated for the detection of secondary forms of hypertension. Apart from clinical and routine laboratroy investigation in each, straight film of abdomen, intravenous pyelography (IVP), isotope renography and aortography were done in 174, 51, 109 and 2 cases respectively. Evidences of secondary hypertension was present in 22(7.8%) of which renal aetiology was probable in all but 4. Of the 10 patients with a primary kidney condition, possible renal aetiology was unsuspected in only one patient with unilateral renal hypoplasia. In 8 patients with renal involvement due to systemic disease, or in 4 with non-renal causes, the aetiological diagnosis was suggested by the clinical situation. In view of low yield of curable hypertension and high cost, IVP and renography should only be employed selectively and not as routine investigations.

Adult↗
PubMed1976

Mild hypertension--a review of 126 cases.

One hundred and twenty-six patients (71 non-diabetics and 55 diabetics) suffering from mild hypertension (Diastolic BP 90-110) have been reviewed. Hypertension was idiopathic in 123 and possible renal causes were considered in 3 cases. Evidence of target organ involvement, either singly or in combination in the form of electrocardiographic evidence of left ventricular hypertrophy and ischaemic changes, cardiac enlargement on radiology, cerebrovascular insufficiency, retinopathy and albuminuria in the absence of other pre-disposing causes was present in 28.5% of the patients. The prevalence rate of these complications was higher in the diabetics (34.5%) as compared to non-diabetics (23.9%). These complications occurred in the 4th and 5th decades of life in nearly 80% of these patients. Serum cholesterol was higher in diabetic patients with complications than non-diabetics. Mild hypertension may not be an entirely benign condition and the need for controlled studies to assess the efficacy of anti-hypertensive drugs in this category is stressed.

Adult↗
PubMedDate not supplied

Extrinsic obstruction of a Carbomedics prosthesis in the mitral position: echocardiographic and surgical findings.

In this article a case of malfunction of a Carbomedics mitral prosthesis in a patient with mild symptoms is described. Although there was evidence by echocardiography of a thrombus in proximity to the prosthesis and leaflet immobility assumed to be caused by the thrombus, it was demonstrated, at the time of surgery, that the immobility of the prosthetic leaflet was due to a chorda tendineae stuck between the leaflet and the sewing ring. This is the first report of this occurring in a bileaflet prosthesis. It is likely that the restricted mobility of the leaflet had contributed to the thrombosis of the prosthesis.

Adult↗