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Biomedical subjects

A D Timmis

Publications and source records attributed to A D Timmis.

At least 145 records · Page 8Linked to original sources
PubMed1985

Progression of cardiovascular disease in acromegalic patients treated by external pituitary irradiation.

Cardiovascular complications are a major cause of morbidity and mortality in acromegaly and seem to be related to the long duration of the disorder. Conventional external pituitary irradiation for acromegaly produces a consistent, but slow, fall in elevated serum growth hormone (GH) levels. It has not been established whether such treatment is effective in preventing the development of cardiovascular complications. The evolution of cardiovascular disease has therefore been studied in 11 acromegalic patients followed up for a mean 10 years (range 3-17) after external pituitary irradiation. At the final follow-up fasting serum GH were significantly (P less than 0.01) lower than pre-irradiation levels, but cardiovascular events (myocardial infarction, dysrhythmias, hypertension, major arterial disease, heart failure) increased significantly in prevalence (P less than 0.01) during this period. Electrocardiographic abnormalities also increased in prevalence. At the final follow-up 6 patients had cardiomegaly on chest X-ray and echocardiographs (10 patients) were abnormal in every case. All 11 patients had evidence of complete or partial anterior hypopituitarism. We confirm that external pituitary irradiation is effective in reducing elevated serum GH levels in acromegaly, but suggest that such a slow reduction in serum GH levels does not retard the development of cardiovascular complications.

Acromegaly↗
PubMed1985

Studies with felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. Its potential role in the treatment of congestive heart failure was examined in short and long term oral studies. Short term felodipine 5 to 15 mg in 11 patients increased (p less than 0.001) cardiac index (from 2.1 +/- 0.1 to 3.3 +/- 0.2 L/min/m2), and reduced systemic resistance (from 26 +/- 2 to 12 +/- 2 units) and left ventricular end-diastolic pressure (from 26 +/- 2 to 13 +/- 2mm Hg) without affecting heart rate. Left ventricular max dp/dt did not change, but max dp/dt/p increased from 19 +/- 1 to 24 +/- 1 sec-1 (p less than 0.001). Left ventricular unloading was reflected by a shift in the end-systolic pressure-dimension relationship downwards and to the left. Myocardial oxygen supply to demand ratio improved significantly; coronary flow increased from 141 +/- 11 to 176 +/- 15 ml/min and myocardial oxygen consumption fell from 18 +/- 2 to 14 +/- 1 ml/min (p less than 0.05). Long term therapy with felodipine 30 mg daily in 10 patients improved treadmill exercise tolerance after 4 weeks by 24% (p less than 0.001). Stroke index at submaximal exercise increased from 37 +/- 3 to 47 +/- 2 ml/beat/m2 (p less than 0.001). Pulmonary capillary wedge pressure fell significantly (22 +/- 5 to 10 +/- 3mm Hg), as did arteriovenous oxygen difference (12.7 +/- 0.9 to 9.7 +/- 0.6 vols/100ml). Importantly, these beneficial effects with felodipine were sustained during 4 weeks' therapy without evidence of tachyphylaxis. These data indicate that the selective vasodilator properties of felodipine may extend the clinical application of calcium antagonists to include the management of heart failure.

Aged↗
PubMed1984

Potential value of oral beta 2-adrenoceptor agonists in congestive heart failure: a haemodynamic and metabolic study.

This study was designed to investigate and compare the haemodynamic and metabolic responses to pirbuterol and salbutamol in patients with congestive heart failure and coronary artery disease. Attention was directed towards the effects these beta 2-adrenoceptor agonists have on left ventricular systolic function, systemic and coronary haemodynamics and myocardial substrate metabolism. Sixteen patients were randomly allocated to treatment with either pirbuterol 20 mg or salbutamol 6 mg. Since no statistically significant differences between the responses to these drugs were observed, combined data for both agents are presented. Ninety minutes after the drug intervention cardiac index increased from 2.2 +/- 0.1 to 2.9 +/- 0.2 1/min per m2 (P less than 0.001) in association with marked reductions in systemic vascular resistance (from 22 +/- 1 to 15 +/- 1 units, P less than 0.001) and increments in left ventricular dp/dtmax (from 1074 +/- 85 to 1422 +/- 133 mm Hg/sec, P less than 0.05). Modest reductions in left ventricular end-diastolic pressure (from 21 +/- 1 to 15 +/- 1 mm Hg, P less than 0.01) were observed. Heart rate increased from 82 +/- 5 to 91 +/- 4 beats/min (P less than 0.01) but the small fall in mean arterial pressure (from 86 +/- 3 to 78 +/- 3 mm Hg) was not significant. Drug-induced coronary vasodilatation reduced coronary coronary vascular resistance from 0.65 +/- 0.06 to 0.47 +/- 0.04 units (P less than 0.01) and led to a marked increase in coronary sinus blood flow (from 124 +/- 9 to 155 +/- 9 ml/min, P less than 0.05). Arterial levels of free fatty acids increased from 0.78 +/- 0.13 to 1.05 +/- 0.18 mmol/l (P less than 0.05) resulting in the preferential utilization of this substrate as a myocardial energy source. Despite the substantial haemodynamic improvement, however, no significant increase in myocardial oxygen uptake or lactate production was observed. Thus, in patients with coronary artery disease and congestive heart failure pirbuterol and salbutamol improve left ventricular function by a combination of afterload reduction and positive inotropism such that no appreciable deterioration in myocardial energetics occurs.

Adult↗
PubMed1984

Restoration of normal reflex responses to orthostatic stress during felodipine therapy in congestive heart failure.

The mechanisms underlying the abnormal responses to orthostatic stress in congestive heart failure are ill defined and little is known about the effects of specific therapy. In the present study intravascular pressures and plasma noradrenaline levels were measured in nine patients with heart failure subjected to 45 degrees and 90 degrees upright tilt. Studies were repeated during 4 weeks of vasodilator therapy with felodipine and again after felodipine withdrawal. Before the introduction of vasodilator therapy, tilt did not activate orthostatic reflexes despite significant reductions in left ventricular filling pressure and cardiac output. Thus, plasma noradrenaline, heart rate and systemic vascular resistance were unaffected and blood pressure fell. Felodipine resulted in a rapid and sustained improvement in left ventricular function but restoration of orthostatic reflexes was delayed and could be detected only after 48 h therapy. At this time, and during the subsequent 4 weeks, tilt-induced reductions in ventricular filling and cardiac output produced a normal rise in plasma noradrenaline and heart rate. A postural drop in blood pressure, however, was not averted because the direct action of felodipine on vascular smooth muscle prevented adrenergically-mediated increments in systemic vascular resistance. Felodipine withdrawal led to a prompt deterioration in left ventricular function. Orthostatic reflexes, however, were still intact 48 h later when tilt elicited a completely normal pattern of responses. These observations confirm that the abnormal responses to orthostatic stress in congestive heart failure are due principally to impairment of autonomic control mechanisms and are not related to the absence of venous pooling. Importantly the autonomic dysfunction is reversible with felodipine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Acute haemodynamic and metabolic effects of felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.

Adult↗
PubMed1984

Single lead atrial synchronised pacing in patients with cardiogenic shock after acute myocardial infarction.

A pacing system requiring only a single lead was used to establish atrial synchronised pacing in eight patients with complete atrioventricular block and cardiogenic shock following acute myocardial infarction. Spontaneous atrial activity was sensed through electrodes positioned on the pacing lead and used to trigger ventricular demand pacing. A normal atrioventricular relation could be established in each of these critically ill patients without the complexity of inserting and finding a stable position for an additional atrial sensing lead. Atrial synchronised pacing at the spontaneous sinus rate had distinct haemodynamic advantages compared with conventional ventricular pacing at 100 beats/min. Mean cardiac output for the group was 3.3 1/min with atrial synchronised pacing compared with 2.6 1/min with conventional pacing, a significant difference of 27%. Peak systolic pressure averaged respectively 91 and 73 mm Hg in the two pacing modes. With conventional ventricular pacing a pronounced phasic alteration in blood pressure was observed, dependent on the altering relation of the paced beats to spontaneous atrial activity. Atrial synchronised pacing abolished this effect and resulted in a stable blood pressure at or above the peak pressure achieved with conventional pacing. Atrial synchronised pacing with a single lead system can be established rapidly. This mode of pacing has appreciable and significant haemodynamic superiority over conventional ventricular pacing in patients with cardiogenic shock and atrioventricular block following acute myocardial infarction.

Aged↗
PubMed1984

Effects of vasodilator treatment with felodipine on haemodynamic responses to treadmill exercise in congestive heart failure.

Treatment with vasodilators in heart failure has not always produced a useful improvement in the haemodynamic responses to exercise, and in many cases early drug tolerance has further limited the potential of this type of treatment. In a study to evaluate the efficacy of felodipine, a new calcium antagonist with selective vasodilator properties, in the management of congestive heart failure 10 patients with congestive heart failure underwent treadmill exercise testing before and during oral treatment with felodipine 30 mg daily. At every level of exercise felodipine lowered the pulmonary capillary wedge pressure, whereas cardiac index and stroke index increased considerably. The haemodynamic improvement was associated with an increase in the duration of exercise to exhaustion. Importantly, these beneficial effects were sustained throughout four weeks of treatment without evidence of drug tolerance. These observations suggest a useful role for felodipine in the long term management of congestive heart failure.

Adult↗
PubMed1982

Comparison of haemodynamic responses to dobutamine and salbutamol in cardiogenic shock after acute myocardial infarction.

Nine patients with critically reduced cardiac output after acute myocardial infarction underwent a single cross-over comparison of dobutamine and salbutamol to compare the haemodynamic effects of these drugs, which have, respectively, predominantly beta 1-adrenergic and beta 2-adrenergic agonist activity. The responses were used to select the more appropriate treatment for individual patients. Only relatively small responses were obtained: those with poorest baseline measurements tended to show the least effect. When the results from the series were averaged, dobutamine (250-750 microgram/min) caused a small but progressive increase in cardiac index (1.8 to 2.2 1/min/m2) throughout the dose range. Systemic blood pressure was not increased, and calculated systemic vascular resistance fell from 25 to 19 units. Heart rate rose from 107 to 118 beats/min and stroke index from 17 to 19 ml/beat/m2. Pulmonary artery end-diastolic pressure fell from 18 to 15 mm Hg. Salbutamol (10-40 microgram/min) produced a similar progressive increase in cardiac index, from 1.6 to 2.21/min/m2. Systemic blood pressure was not altered, and systemic vascular resistance fell from 25 to 20 units. Heart rate rose from 105 to 119 beats/min and stroke index from 16 to 19 ml/beat/m2. Pulmonary artery end-diastolic pressure did not fall. Dobutamine and salbutamol have closely similar haemodynamic effects when used in cardiogenic shock after acute myocardial infarction. Both drugs increase cardiac index but heart rate also rises, and the increase in stroke index is relatively small. Mean arterial pressure is altered little by either agent, but dobutamine (in contrast with dopamine) tends to reduce pulmonary artery end-diastolic pressure, which may be beneficial.

Aged↗
PubMed1982

Role of labetalol in acute myocardial infarction.

1 The role of labetalol in managing acute myocardial infarction is reviewed. 2 After intravenous infusion labetalol lowers blood pressure in patients with increased blood pressure associated with acute myocardial infarction. 3 Although average heart rate was decreased, cardiac index fell only slightly and stroke index was substantially unchanged. 4 In patients whose pretreatment pulmonary artery end-diastolic pressures were increased, labetalol induced decreases, whereas in the presence of normal pressures, these were unchanged. 5 It is concluded that labetalol infusion in patients with acute myocardial infarction is unlikely to precipitate heart failure and is likely to be of value in reducing myocardial oxygen requirement.

Acute Disease↗
PubMed1982

The influence of hemodialysis fistulas on circulatory dynamics and left ventricular function.

This study was designed to examine the influence of arteriovenous (A-V) fistulas on cardiac output and left ventricular performance in 13 uremic patients on regular hemodialysis. M-mode echocardiography and systolic time intervals were used to derive indices of left ventricular function, and cardiac output was measured by thermodilution. Measurements were performed before and after acute digital occlusion of the A-V fistulas. Occlusion of a single fistula caused systemic vascular resistance and the systolic diameter of the left ventricle to increase from 9.6 +/- 1 to 13.5 +/- 2 units (p less than 0.001) and from 3.2 +/- .3 to 3.4 +/- .4 (p less than 0.05) respectively. The increase in afterload caused a reduction in cardiac output from 11.0 +/- 1 to 9.6 +/- 1 l/min (p less than 0.001) and probably accounted for the minor, though not significant, "deterioration" in the indices of left ventricular function. Bilateral fistula occlusion in 8 patients exaggerated these changes, and the reduction in fractional shortening from 43 +/- 4 to 37 +/- 4% was significant at the 5% level. In two patients with severe left ventricular failure, fistula occlusion caused a more pronounced deterioration in cardiac performance. These results show that acute A-V fistula occlusion effectively lowers cardiac output and is, therefore, likely to be beneficial in the management of high output failure. However, when intrinsic left ventricular disease is the primary etiological factor in heart failure, fistula occlusion is unlikely to be helpful, and may worsen the hemodynamic derangement.

Adult↗
PubMed1981

Pulmonary oedema without critical increase in left atrial pressure in acute myocardial infarction.

Twelve patients with acute myocardial infarction and radiological evidence of pulmonary oedema were observed in whom the left atrial pressure, measured indirectly as pulmonary artery end-diastolic pressure, was not critically increased (range 5-12 mm Hg with reference to sternal angle). Eight of the patients had been treated with frusemide, but only six had responded: hence in at least half of the series diuresis could not account for the anomalous finding. Six patients with low cardiac output were given infusions to expand plasma volume. Appreciable increments in mean values for cardiac index (1.6 to 2.0 1/min/m2), stroke index (18 to 23 ml/beat/m2), mean arterial pressure (65 to 86 mm Hg), and pulmonary artery end-diastolic pressure (8 to 15 mm Hg) were recorded. This group, and the remaining six patients with higher cardiac output, survived to leave hospital. Delay in radiographic clearing after a fall of left atrial pressure was a possible explanation for the relatively low pulmonary artery end-diastolic pressures, especially in the patients treated successfully with diuretics. Other mechanisms, such as alterations in pulmonary vascular permeability, might also have contributed to the syndrome. Pulmonary oedema without a critical increase in the left atrial pressure is unusual in acute myocardial infarction but the therapeutic implications are important. Withdrawal;of diuretics may be indicated, and in some cases expansion of plasma volume may lead to striking clinical improvement.

Aged↗
PubMed1981

Comparison of haemodynamic responses to dopamine and salbutamol in severe cardiogenic shock complicating acute myocardial infarction.

Twelve patients with severe persistent cardiogenic shock complicating acute myocardial infarction underwent single crossover treatment with intravenous dopamine and salbutamol to determine the more beneficial therapy. Salbutamol (10 to 40 microgram/min) reduced systemic vascular resistance and progressively increased both cardiac index and stroke index. Heart rate increased from 95 to 104 beats/min. Changes in mean arterial pressure and pulmonary artery end-diastolic pressure were small and insignificant. Dopamine infusion at rates of 200 and 400 micrograms/min also increased cardiac index and stroke index. Systemic vascular resistance fell slightly but mean arterial pressure rose from 57 to 65 mm Hg. Heart rate increased from 95 to 105 beats/min. Changes in pulmonary artery end-diastolic pressure were again small and insignificant. Dopamine infusion at 800 micrograms/min caused an appreciable increase in systemic vascular resistance; a further increment in mean arterial pressure was observed, though cardiac index fell slightly. Heart rate and pulmonary artery end-diastolic pressure rose steeply. Salbutamol, a vasodilator, increased cardiac output in patients with cardiogenic shock complicating acute myocardial infarction but did not influence blood pressure. If correction of hypotension is essential dopamine in low doses may be the preferred agent. Doses of 800 microgram/min, which is within the therapeutic range, worsen other manifestations of left ventricular dysfunction.

Albuterol↗
PubMed1981

The influence of 1 alpha-hydroxycholecalciferol on left ventricular function in end-stage renal failure.

This study was designed to assess the influence of 1 alpha-hydroxycholecalciferol on left ventricular function in end-stage renal failure. Twelve patients, all of whom were on regular haemodialysis, were investigated. M-mode echocardiography and systolic time intervals were used to derive indices of left ventricular function. Measurements were performed before and six weeks after treatment with one microgram daily of 1 alpha-hydroxycholecalciferol. Fractional fibre shortening increased from 34.6 to 37.6% (p less than 0.025) and mean velocity of fibre shortening increased from 1.21 to 1.32 circ/sec (p less than 0.01). These changes were associated with a fall in the mean plasma parathyroid hormone concentration from 1883 to 1123ng/L (p less than 0.0025) and a rise in magnesium concentration from 0.89 to 1.06 mmol/L (p less than 0.0025); plasma calcium increased from 2.59 to 2.70mmol/L but this change was not significant. Our results indicate that 1 alpha-hydroxycholecalciferol improves left ventricular function in end-stage renal failure by influencing both the turnover or secretion of parathyroid hormone and the metabolism of calcium and magnesium ions.

Adult↗