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Biomedical subjects

M Packer

Publications and source records attributed to M Packer.

144 records · Page 8Linked to original sources
PubMed1981

Quantification of valve regurgitation by radionuclide angiography before and after valve replacement surgery.

Radionuclide gated cardiac blood pool imaging was used to quantify the severity of valve regurgitation in 20 patients, by calculating the ratio of left ventricular to right ventricular stroke counts (end-diastolic minus end-systolic counts in right and left ventricular regions of interest). This ratio (the stroke index ratio) was substantially higher in patients with aortic and mitral regurgitation (3.91 +/- 1.45) than in a control group of 10 patients without regurgitation (1.32 +/- 0.15), p less than 0.001. The stroke index ratio correlated closely (r = 0.947) with measurements of regurgitant fraction derived from simultaneous determinations of total and forward stroke volumes during cardiac catheterization. After aortic and mitral valve replacement in 18 patients, the stroke index ratio decreased from 4.03 +/- 1.46 to 1.38 +/- 0.23 (p less than 0.001), a value not significantly different from that observed in patients without regurgitation. All three patients with residual postoperative regurgitation had a stroke index ratio greater than 2 standard deviations above the mean values for the control group (greater than 1.62), whereas the remaining 15 patients, who had no evidence of regurgitation, had values within the normal range. Therefore, radionuclide gated blood pool scanning provides a noninvasive method of quantifying valve regurgitation and assessing the results of medical or surgical interventions.

Adult↗
PubMed1981

Sustained effectiveness of minoxidil in heart failure after development of tolerance to other vasodilator drugs.

Although a variety of vasodilator drugs produce acute hemodynamic improvement in patients with severe chronic heart failure, long-term treatment with these agents may be associated with the development of drug tolerance and loss of initial beneficial effects. Five serial right heart catheterizations in a 78 year old man with severe chronic heart failure due to idiopathic cardiomyopathy documented the development of hemodynamic and clinical tolerance to oral hydralazine and oral captopril after initial responses were observed to both agents. However, sustained hemodynamic and clinical improvement by invasive testing was noted with minoxidil (20 mg orally twice daily) after 4 and 9 weeks of continuous therapy. These observations indicate that pharmacologic tolerance may occur with a variety of vasodilator drugs and may account for the failure of some patients to improve clinically with long-term therapy despite initial favorable hemodynamic effects. However, such tolerance seems to be drug-specific and, hence, its recognition in an individual patient does not prelude responsiveness to other vasodilator agents.

Administration, Oral↗
PubMed1981

Determinants of drug response in severe chronic heart failure. 1. Activation of vasoconstrictor forces during vasodilator therapy.

Vasodilator drugs activate neurohumoral forces that produce peripheral vasoconstriction and tachycardia and probably cause the rebound events observed upon abrupt withdrawal of therapy. To determine their role in limiting therapeutic vasodilator responses, these reactive forces were measured in 40 patients with severe chronic heart failure by quantifying the magnitude of rebound change (MRC) after nitroprusside withdrawal. Group 1 patients (n = 22), who had minimal reactive vasoconstriction (MRC less than or equal to 27%), showed marked hemodynamic effects with nitroprusside (4.5 microgram/kg/min) and isosorbide dinitrate (40 mg orally), associated with significant decreases in heart rate with both drugs (p less than 0.001). Despite administration of the same doses of both drugs, group 2 patients (n = 18), who had marked rebound changes (MRC greater than 27%), showed significantly smaller changes in cardiac index, systemic vascular resistance and mean arterial pressure (p less than 0.001), associated with no change or increases in heart rate. Rebound events were attenuated and the responses to nitroprusside and nitrates were enhanced in four patients in whom these drugs were readministered after pretreatment with i.v. phentolamine (0.3mg/min). We conclude that activation of neurohumoral forces can limit the hemodynamic responses to vasodilator administration; this supports the use of combination therapy of direct-acting vasodilators and neurohumoral antagonists in selected patients with severe chronic heart failure.

Administration, Oral↗
PubMed1980

Importance of left ventricular chamber size in determining the response to hydralazine in severe chronic heart failure.

To examine the importance of left ventricular chamber size in determing the response to vasodilator therapy, we performed echocardiography in 40 patients with chronic refractory heart failure before they were treated with oral hydralazine. The left ventricular end-diastolic dimension (LVEDD) correlated significantly with the per cent change in stroke volume (r = 0.77), left ventricular filling pressure (r = -0.68), and stroke work index (r = 0.87) during short-term drug administration. After 14 to 21 days of maintenance therapy, 15 of 24 patients with an LVEDD greater than or equal to 60 mm were improved, and one was worse; mean blood urea nitrogen decreased from 45.6 to 30.6 mg per deciliter in the 21 patients in this group who completed the study (16.3 to 10.9 mmol per liter) (P less than 0.001). In contrast, only two of 16 patients with an LVEDD less than 60 mm improved, whereas 10 showed clinical deterioration; blood urea nitrogen increased from 49.3 to 64.2 mg per deciliter in the 13 patients in this group who completed the study (17.6 to 22.9 mmol per liter) (P less than 0.01). These findings indicate that left ventricular chamber size is an important factor in the response to hydralazine in patients with severe chronic heart failure.

Administration, Oral↗
PubMed1980

Hemodynamic evaluation of hydralazine dosage in refractory heart failure.

Hemodynamic responses to different doses of hydralazine were evaluated in 18 patients with severe refractory resistant heart failure. There were no significant overall hemodynamic effects after 50 mg hydralazine. After 75 mg, CI increased slightly (+0.36 l/min/m2) with a 19% decrease in SVR. After 100 mg, there were substantial increases in CI (+0.60 l/min/m2) and decreases in SVR (31%) changes which were greater than those after 75 mg, but the decrease in MAP with 100 mg (-6.6 mm Hg) was of the same order as that after 75 mg (-5.0 mm Hg). LVFP and SWI improved significantly only with 100-mg doses. Seven patients in whom 100 mg hydralazine induced no hemodynamic effects all responded to single doses of 150 to 200 mg. The duration of action of hydralazine was longer (p less than 0.001) in patients with a CCr less than 35 ml/min (14.3 +/- 1.4 hr) than in patients with adequate renal function (7.9 +/- 0.5 hr). Thus, the dose and dosing interval of hydralazine needed to induce hemodynamic improvement in patients with severe heart failure are variable and require individualization.

Aged↗
PubMed1979

Rebound hemodynamic events after the abrupt withdrawal of nitroprusside in patients with severe chronic heart failure.

We studied the hemodynamic events that followed abrupt withdrawal of nitroprusside in 20 patients with severe chronic heart failure. With nitroprusside, cardiac index increased from 1.96 to 2.87 liters per minute per square meter of body-surface area, but it decreased to 1.66 (P less than 0.001) after withdrawal of nitroprusside. Left ventricular filling pressure and systemic vascular resistance decreased from 23.9 to 15.3 mm Hg and from 1642 to 921 dyn.sec.cm-5, respectively, with nitroprusside, but increased to 30.4 mm Hg and 2109 dyn.sec.cm-5 (both P less than 0.001) upon its discontinuation. These rebound changes were maximal 10 to 30 minutes after nitroprusside withdrawal and returned to control levels one to three hours later. Although in 17 of 20 patients, these rebound changes caused no or minimal exacerbation of symptoms, pulmonary edema, which resolved in three patients. Activation of reflex vasoconstrictive forces during vasodilator therapy may explain these effects of withdrawal.

Adult↗
PubMed1979

Prognostic value of echocardiographic evaluation of septal function in acute anteroseptal myocardial infarction.

To determine the clinical usefulness of echocardiography in patients with anteroseptal myocardial infarction, echocardiograms were performed within 24 hours of admission on 40 patients with acute transmural anteroseptal myocardial infarction. Twenty-one patients had normal septal motion and septal systolic thickening, and 19 patients had abnormalities of one or both of these measurements. Of the 21 patients who had normal septal motion and thickening, only five developed congestive heart failure, none developed bundle branch block, and none died. Of the 19 patients with abnormal septal motion and/or thickening, 17 developed congestive heart failure (p less than .001), seven developed bundle branch block (p less than .001), and six died (p less than .001). Therefore, (1) electrocardiographic evidence of septal infarction does not correlate with abnormalities of the portion of septum seen on echocardiogram, and (2) patients with anteroseptal myocardial infarction and abnormalities of the septum on echocardiogram have more complications and a higher in-hospital mortality rate. These patients may have more extensive myocardial infarction predisposing to pump failure and possibly involving the conduction system.

Aged↗
PubMed1979

Differences in hemodynamic effects of nitroprusside and prazosin in severe chronic congestive heart failure: evidence for a direct negative chronotropic effect of prazosin.

To compare the hemodynamic effects of prazosin and nitroprusside in patients with severe congestive heart failure, nine patients with heart failure refractory to conventional therapy received oral prazosin and intravenous nitroprusside administered so as to produce a similar decrease in left ventricular filling pressure in each patient. By this comparison, both drugs produced similar decreases in mean right atrial pressure, mean pulmonary arterial pressure and systemic and pulmonary vascular resistance. However, with nitroprusside, cardiac index increased more (+0.97 versus +0.73 liters/min per m2, P less than 0.01) and mean arterial pressure decreased less (-13.7 versus -18.3 mm Hg, P less than 0.05) than with prazosin. Both drugs produced similar changes in stroke volume index (+11.7 cc/beat per m2 with nitroprusside and +12.5 with prazosin) and stroke work index (+8.1 g-m/m2 with nitroprusside and +6.6 with prazosin). Therefore, the differences in the hemodynamic responses observed with the two agents were due to the significantly greater decrease in heart rate with prazosin (-8 beats/min) than with nitroprusside (-2 beats/min, P less than 0.05). These clinical data support experimental evidence suggesting that there is a significant negative chronotropic action of prazosin independent of its peripheral vascular effects.

Administration, Oral↗
PubMed1979

The effects of maternally administered pethidine or epidural bupivacaine on the fetus and newborn.

The continuous fetal heart rate rate pattern, condition of the baby at birth and its subsequent behaviour were compared in three groups of infants whose mothers received during labour either no drugs, intramuscular pethidine or epidural bupivacaine. The blood levels of pethidine and bupivacaine were measured at delivery in a maternal vein, and umbilical artery and vein, and in the newborn during the first 48 hours of life. The only significant changes in the fetal heart rate pattern occurred in association with maternal hypotension or uterine hyperstimulation. The Apgar scores at one minutes were 7 or less in more infants in the intramuscular pethidine and epidural bupivacaine groups as compared with the controls. There were no differences in the Apgar scores at five minutes. Neonatal behaviour during the first six weeks of life was not significantly affected by pethidine or epidural bupivacaine when compared with the control group. Pethidine and bupivacaine were shown to cross the placenta freely. The half-life of these drugs in the newborn was longer than in the adult.

Anesthesia, Epidural↗
PubMedDate not supplied

Physiologic and pharmacologic determinants of vasodilator response: a conceptual framework for rational drug therapy for chronic heart failure.

This article has attempted to summarize the increasing number of pharmacologic and physiologic variables that are being recognized as important determinants in the response to vasodilator therapy in patients with severe chronic heart failure. It is apparent that a careful consideration of many factors is necessary before proper selection of a specific drug can be made for a specific patient, since not all patients with refractory heart failure demonstrate beneficial hemodynamic and clinical responses to all agents. Each patient presents us with a unique set of physiologic variables; each drug has its own advantages and limitations. Identification of those subgroups of patients most likely to benefit from a specific agent or combination of agents is a major goal for future research. Although a number of hemodynamic variables can be made to improve acutely with a wide variety of vasodilator drugs, well tolerated sustained meaningful clinical benefits are probably observed in relatively few patients. Rational and successful vasodilator therapy is possible only through a highly individualized approach.

Antihypertensive Agents↗
PubMedDate not supplied

Ophthalmology's botanical heritage.

Many of today's important ophthalmic pharmaceuticals have a rich ethnobotanical history. Solanaceous plants, the source of atropine, have contributed to medical therapy since the beginning of Western civilization. The botanical source of physostigmine played a pivotal role as an ordeal poison in the culture of Old Calabar, West Africa. Native peoples of Amazonia treasured plants containing pilocarpine as panaceas because of their impressive diaphoretic effect. Nineteenth century scientists examining these plants because of their folkloric reputations discovered their active compounds and documented their physiological effects. Ophthalmologists such as Argyll Robertson, Laqueur, and Weber built upon this research to bring these pharmaceuticals into therapeutic use. The ongoing loss of the world's tropical rain forests threatens to destroy a vast storehouse of untested biological compounds.

Glaucoma↗