Tratamiento hormonal sustitutivo y cardiopatía isquémica en la mujer / Hormone replacement therapy and ischemic heart disease in women

El tratamiento hormonal sustitutivo es un tema controvertido puesto que si bien existen estudios observacionales que demuestran que reduce el riesgo de padecer enfermedad coronaria, principalmente por su acción favorable sobre los lípidos, aún no está comprobado que prevengan la enfermedad cardiovascular. Se hace una revisión de los ensayos realizados con el propósito de analizar el efecto del tratamiento hormonal sustitutivo en la prevención primaria y secundaria de la cardiopatía isquémica, incluyendo los moduladores selectivos de los receptores de estrógenos y los fitoestrógenos. Se concluye que ante la necesidad de prescribir THS es necesario individualizar cada caso; no hay evidencias de que sea útil iniciarlo como prevención secundaria en pacientes isquémicas y que el control de los factores de riesgo sigue siendo el principal aspecto en la prevención de la cardiopatía isquémica y debe aconsejarse a toda mujer menopáusica. (AU)

Cardiac cellular actions of hydrochlorothiazide.

In long term treatment, thiazide diuretics such as hydrochlorothiazide (HCTZ) lower blood pressure by decreasing peripheral resistance rather than by their diuretic effect. This action has been attributed to the opening of Ca2+-activated K+ channels in vascular smooth muscle cells. However, little is known about their cardiac cellular actions. Here we investigated the possible actions of HCTZ on action potential and contraction of rat ventricular muscle strips and on the ionic currents of isolated rat ventricular cardiomyocytes. HCTZ depressed ventricular contraction with an IC30 of 1.85 microM (60% decrease at 100 microM). Action potential duration at -60 mV and maximal rate of depolarization were, however, only slightly decreased by 12% and 22%, respectively, at 100 microM. At the single cell level, HCTZ (100 microM) depressed the fast Na+ current (INa) and the L-type Ca2+ current (ICaL) by 30% and 20%, respectively. The effects on ICaL were not voltage-or frequency-dependent. In cells intracellularly perfused with 50 microM cyclic adenosine, monophosphate HCTZ reduced ICaL by 33%. The transient (Ito), the delayed rectifier and the inward rectifier potassium currents were decreased by 20% at 100 microM HCTZ. The effects on Ito were voltage-dependent. In conclusion, HCTZ at high concentrations possesses a negative inotropic action that could be in part due to its blocking action on INa and ICaL. The actions of HCTZ on multiple cardiac ionic currents could explain its weak effect on action potential duration.

[Dual isotope myocardial scintigraphy (201thallium at rest/99 M technetium tetrofosmin with exercise) in the detection of reversible hypoperfusion]. / Gammagrafía miocárdica con doble isótopo (201Tl en reposo/ 99mTc-tetrofosmin en esfuerzo) en la detección de hipoperfusión reversible.

The dual-isotope technique (rest 201Tl and stress 99mTc-sestamibi) is useful to assess myocardial perfusion in coronary disease patients. 99mTc-labeled tetrofosmin is a radiopharmaceutical whose characteristics are similar to sestamibi. Thus, we decided to use it to detect reversible myocardial hypoperfusion in patients with a background of myocardial infarction and ischemia. A sequential dual-isotope scintigraphy (3 mCi rest 201Tl and 25 mCi stress 99mTc-tetrofosmin) with 24-hour 201Tl redistribution (RD) was performed in 20 patients with previously confirmed myocardial infarction and clinical and ergometric signs of ischemia. Each patient also underwent a stress-redistribution protocol with redistribution at 4 and 24 hours post injection with 201Tl scintigraphy within two weeks of the first study. The qualitative uptake analysis showed no significant differences in the number of myocardial segments with severe reduction of tracer uptake on stress that improved at rest or in RD images, even if 24-hour RD images were considered. The quantitative global uptake analysis showed a similar defect reversibility with both protocols; however if 24-hour RD images were considered the uptake improvement was significant only when compared with the rest 201Tl images in dual-isotope scintigraphy protocol (75+/-8% vs. 81+/-9% of peak activity, rest vs. 24-hour RD; p<0.01) and not when compared with the 4-hour RD in the 201Tl scintigraphy. On the other hand, when only the segments with severely reduced uptake (<50% of peak activity) were analyzed, the 24-hour RD improved myocardial uptake significantly (p<0.001 vs. rest and vs 4-hour RD) in both protocols. We conclude that a sequential dual-isotope rest 201Tl/stress 99mTc-tetrofosmin scintigraphy is comparable with stress-redistribution 201Tl scintigraphy to detect reversible myocardial hypoperfusion; however in both cases, the addition of 24-hour images increases its usefulness in severely hypoperfused segments, if the uptake of the radiopharmaceutic is quantified.

Gammagrafía miocárdica con doble isótopo (201Tl en reposo/ 99m Tc-tetrofosmin en esfuerzo) en la detección de hipoperfusión reversible / Dual isotope myocardial scintigraphy (201TI at rest/99m Tc tetrofosmin on stress) in the detection of reversible hypoperfusion

La técnica de doble isótopo (201Tl en reposo/99mTc sestamibi en estrés) es útil para evaluar la perfusión miocárdica en pacientes con cardiopatía isquémica.Por otra parte, el 99mTc-tetrofosmin es un radiofármaco con características similares al sestamibi, por lo que decidimos usarlo para detectar hipoperfusión miocárdica reversible en un grupo de pacientes con antecedentes de infarto de miocardio y manifestaciones de isquemia. Se incluyeron 20 pacientes con infarto de miocardio previo confirmado y signos clínicos y ergométricos de isquemia, a quienes se les hizo una gammagrafía miocárdica secuencial con técnica de doble isótopo (3 mCi de 201Tl en reposo y 25 mCi de 99m Tc-tetrofosmin en esfuerzo). A cada paciente se le hizo también una gammagrafía con 201Tl y protocolo estrés/redistribución (RD) de 4 horas/RD de 24 horas, dentro de las dos semanas posteriores al primer estudio. Cualitativamente no hubo diferencias significativas en el número de segmentos miocárdicos con severa disminución de la captación del trazador en estrés que mejoraron en las imágenes de reposo o en la RD, aun considerando la RD de 24 horas.Con el análisis cuantitativo global de la captación se encontró una reversibilidad similar del defecto con ambos protocolos, aunque si se consideraban las imágenes de RD de 24 horas, la mejoría de la captación fue significativa sólo comparando con las imágenes de 201Tl en reposo en el protocolo con doble isótopo (75 ñ 8 por ciento vs 81 ñ 9 por ciento de la actividad pico, reposo vs RD de 24 horas; p < 0,01) y no con la RD de 4 horas en la gammagrafía con 201 Tl. Por otra parte, analizando sólo los segmentos con captación severamente disminuida (< 50 por ciento de la actividad pico), en ambos protocolos la RD de 24 horas mejoró la captación miocárdica significativamente (p < 0,001 vs reposo y vs RD de 4 horas).Concluimos que la gammagrafía secuencial con técnica de doble isótopo: 201Tl en reposo/99mTc-tetrofosmin en estrés, es comparable con la gammagrafía con 201Tl con protocolo estrés-redistribución para detectar hipoperfusión miocárdica reversible; pero, en ambos casos, la adición de imágenes de RD de 24 horas incrementa su utilidad, principalmente en segmentos severamente hipoperfundidos, si se cuantifica la captación del radiofármaco. (AU)

The dual-isotope technique (rest 201Tl and stress 99mTc-sestamibi) is useful to assess myocardial perfusion in coronary disease patients. 99mTc-labeled tetrofosmin is a radiopharmaceutical whose characteristics are similar to sestamibi. Thus, we decided to use it to detect reversible myocardial hypoperfusion in patients with a background of myocardial infarction and ischemia. A sequential dual-isotope scintigraphy (3 mCi rest 201Tl and 25 mCi stress 99mTc-tetrofosmin) with 24-hour 201Tl redistribution (RD) was performed in 20 patients with previously confirmed myocardial infarction and clinical and ergometric signs of ischemia. Each patient also underwent a stress-redistribution protocol with redistribution at 4 and 24 hours post injection with 201Tl scintigraphy within two weeks of the first study. The qualitative uptake analysis showed no significant differences in the number of myocardial segments with severe reduction of tracer uptake on stress that improved at rest or in RD images, even if 24-hour RD images were considered. The quantitative global uptake analysis showed a similar defect reversibility with both protocols; however if 24-hour RD images were considered the uptake improvement was significant only when compared with the rest 201Tl images in dual-isotope scintigraphy protocol (75 ± 8% vs 81 ± 9% of peak activity, rest vs 24-hour RD; p < 0.01) and not when compared with the 4-hour RD in the 201Tl scintigraphy. On the other hand, when only the segments with severely reduced uptake (< 50% of peak activity) were analyzed, the 24-hour RD improved myocardial uptake significantly (p < 0.001 vs rest and vs 4-hour RD) in both protocols. We conclude that a sequential dual-isotope rest 201Tl/stress 99mTc-tetrofosmin scintigraphy is comparable with stress-redistribution 201Tl scintigraphy to detect reversible myocardial hypoperfusion; however in both cases, the addition of 24-hour images increases its usefulness in severely hypoperfused segments, if the uptake of the radiopharmaceutic is quantified (AU)

Enhanced detection of reversible myocardial hypoperfusion by technetium 99m-tetrofosmin imaging and first-pass radionuclide angiography after nitroglycerin administration.

BACKGROUND: Reversal of ischemia after myocardial infarction by revascularization is worthwhile only if viability exists in a sufficiently large portion of the left ventricle. METHODS AND RESULTS: To determine myocardial hypoperfusion reversibility and its influence on segmental and global function, we studied 50 patients after myocardial infarction. Three technetium 99m-tetrofosmin scintigraphies were performed: 1 at rest, 1 after 0.6 mg sublingual nitroglycerin (NTG), and 1 after injection at peak stress. First-pass multigated radionuclide angiography was obtained at rest and after NTG. Each patient also underwent a stress redistribution-reinjection thallium-201 scintigraphy. During stress 99mTc-tetrofosmin, 104 segments had normal uptake, 51 showed moderately reduced uptake, and 186 had severely reduced uptake. Of these 186 segments, 33 (18%) improved at rest, and 41 (22%) improved only after NTG. Fifty-nine (79%) of these segments with improved uptake were also found to have reversible defects on 201TI imaging. In the 26 patients with ventricular dysfunction, a 73% agreement was found between the functional and 99mTc-tetrofosmin uptake post-NTG improvement, whereas a 69% agreement was found with thallium reinjection. No significant differences were seen between 99mTc-tetrofosmin and 201T1 imaging. CONCLUSION: Nitroglycerin administration during 99mTc-tetrofosmin scintigraphy improves the detection of myocardium with reversible hypoperfusion in patients with a previous myocardial infarction.

Radionuclide ventriculography in dynamic cardiomyoplasty.

Dynamic cardiomyoplasty improves ventricular function by increasing pump function and by limiting cardiac dilatation. The aim of this study was to assess long-term myocardial performance by radionuclide ventriculography on dilated cardiomyopathy patients subjected to cardiomyoplasty. Thirteen survivors were included. Radionuclide ventriculography was performed one week before surgery and one year later. Five patients were also studied two years following surgery. The left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and ventricular amplitude ratio (VAR) to assess mitral regurgitation were measured. Every case after one year showed a non-significant increase in LVEF. However, the decrease in EDV and in VAR was significant (p < 0.01). No significant difference in these values was found after two years. We conclude that the effects of cardiomyoplasty--reduction of cardiac dilatation, wall stress and mitral regurgitation--are more evident during the first year after surgery. Thereafter, a certain stabilization is observed.

[A comparative study of celiprolol and nicardipine in stable angina of effort]. / Efecto comparativo de celiprolol y nicardipina en angina de esfuerzo estable.

Seventeen patients with effort angina, a positive exercise test and at least one stenosed vessel in coronary angiography were studied. Following a crossover blind-design, each patient received at random either 400 mg/day oral celiprolol or 120 mg/day oral nicardipine. A treadmill exercise test and 24 hour Holter monitoring were accomplished at the end of each treatment period. Both drugs significantly prolonged exercise time and reduced maximum ST segment depression at similar stages of control testing. Nicardipine reduced resting diastolic blood pressure a mean of 18 mm Hg (p less than 0.005) and also systolic blood-pressure 11 mm Hg (p less than 0.005) while celiprolol only reduced systolic pressure 10 mm Hg (p less than 0.01). Resting heart-rate was lowered by celiprolol a mean of 9 beats/min (p less than 0.0001) while nicardipine slightly increased it. The double product at maximum effort decreased with celiprolol and increased with nicardipine. Six patients with 3 vessel disease continued having transient ischemic episodes during treatment with celiprolol and 5 had them with nicardipine. Both drugs were well tolerated by the patients. In conclusion celiprolol and nicardipine proved to be effective in the treatment of myocardial ischemia specially when coronary heart disease is not very advanced.

[Post-infarction recurrent myocardial ischemia. Characterization with Holter ECG and exercise test]. / Isquemia miocárdica recurrente postinfarto. Caracterización por ecg-holter y prueba de esfuerzo.

In order to characterize postinfarction ischemia, 68 patients were studied by 24 hours Holter-monitoring and exercise testing. Twenty-four (35%) patients in Holter-monitoring and 26 (38%) in exercise testing had transient ischemic episodes. A significant coefficient of agreement was found between both tests. Nineteen (79%) of the patients had only silent ischemic episodes in Holter monitoring, and 87% of all episodes were asymptomatic. Twenty-two (87%) of the patients during positive exercise testing had silent ischemia. Eleven (46%) patients had transient ischemia at low and also at high heart-rates. Ten (37%) patients had ischemic episodes at lower charges than 100 watts, and all of them had more than 60 min of total ischemic burden in Holter-monitoring. A significant correlation was found between total ischemic burden and maximum ST segment shifts. The number of ischemic episodes were significantly higher during morning hours. A significantly higher rate of ventricular extrasystoles was found in recurrent ischemic patients, however, no difference was found in complex arrhythmias. After 1 year follow-up, 3 residual ischemic patients have died. The morbidity-calculated relative-risk is 13.9 times higher in patients with recurrent ischemia.

[The hemodynamics of oral nicardipine determined by radioisotope ventriculography in patients with ischemic cardiopathy]. / Hemodinámica de la nicardipina oral determinada por ventriculografía radioisotópica en pacientes con cardiopatía isquemica.

Hemodynamic effects of nicardipine (60 mg) were evaluated in 20 patients whose left ventricular ejection fraction was less than 55%. Nicardipine significantly reduced the mean arterial blood pressure by 28 mmHg (p less than 0.0005). Left ventricular ejection fraction and maximal rate of ventricular diastolic filling were increased in 12% and 84.0 VDF/s (p less than 0.0005) respectively. The end diastolic volume was reduced by 26 ml (p less than 0.001). The decrease in mean arterial blood pressure correlates with the increase in the left ventricular ejection fraction (r = 0.76, p less than 0.001) as well as with the reduced end diastolic volume (R = 0.43, p less than 0.05). The results obtained corroborate the beneficial effects of nicardipine on ventricular function of ischemic patients, whose cardiac reserve is reduced.

Time course of cardiac performance in hypertensive patients after verapamil assessed by nuclear ventriculography.

The effects of oral verapamil monotherapy (320 mg/day) given to a group of essential hypertensive patients (n = 16) on blood pressure, electrocardiogram (ECG) and ventricular function measured by means of nuclear ventriculography (NV) were investigated. Verapamil significantly lowered systolic (SP) (p less than 0.001) and diastolic (DP) (p less than 0.001) blood pressure. Left ventricular ejection fraction (LVEF) and ejection rate (LVER) were reduced from 61.61 +/- 6.34 to 54.16 +/- 6.09% (p less than 0.001) and from 255.6 +/- 58.9 to 217.4 +/- 56.03% (p less than 0.02), respectively. On the other hand, in the right ventricle, the drug only reduced the right ventricular filling rate (RVFR) from 225.2 +/- 60.02 to 167.5 +/- 43.7% (p less than 0.05). Total blood volume (TBV) was also significantly diminished (p less than 0.05). Variations in LVEF (delta LVEF) and RVEF (delta RVEF) correlated with variations in blood pressures and TVB (delta TVB). The results indicate that the hypotensive action mechanism of verapamil could be explained at least in part by a reduction in LVEF and systemic vasodilatation.

Relationships between verapamil plasma concentrations and its antihypertensive action.

Twenty-seven hypertensive outpatients were studied to evaluate the efficacy of verapamil after a single oral dose as well as following a short-term treatment and also in combination with oxprenolol. Blood pressure was significantly reduced (p 0.01) after verapamil monotherapy and the combined treatment. PR interval was lengthened from 30 min to 4 h during acute testing, and also after short-term treatment. QT was only prolonged after the verapamil monotherapy. Systolic time intervals (STIs) were not modified, except left ventricular ejection time (LVETc). Direct correlations were found among verapamil plasma concentrations and changes provoked on blood pressure and PR interval. The mean side effects found were disturbance of atrioventricular conduction in two patients without ulterior complications. The results suggest that verapamil monotherapy or in combination with oxprenolol could be useful in the treatment of essential hypertension.

Spontaneous variability and detection of repetitive extrasystoles during simulated acute antiarrhythmic testing.

In order to estimate the reduction in ventricular premature contractions (VPCs) due to spontaneous variability during simulated acute antiarrhythmic testing, and also to determine the detection capacity for repetitive VPCs during short periods of ECG monitoring usually employed as baseline recordings, 2 groups of patients were studied A reduction by more than 50% of the baseline VPC-rate can be expected to occur as a result of an antiarrhythmic intervention, while approximately 40% of the patients with repetitive high risk VPCs escape detection during short periods of control recordings. It is suggested to use a 24 to 47-hour ambulatory monitoring for the diagnosis and classification of VPCs, while acute antiarrhythmic testing should be employed for assessing individual efficacy and tolerance.

Tecnica de la ventriculografia nuclear. Su valor en cardiopatia isquemica. / Technique of the nuclear ventriculography. Its value in ischemic cardiopathy

Las tecnicas nucleares que emplean camara gamma y computadora digital, han cobrado especial interes en cardiologia durante los ultimos anos.Estos procedimientos presentan como principales ventajas su simplicidad y caracter no invasivo, asi como la informacion que permiten disponer.En el trabajo se presenta la tecnica de ventriculografia nuclear empleada en el laboratorio de los autores y los resultados obtenidos en un grupo de sujetos normales y pacientes con cardiopatia isquemica. Los parametros que se calculan son: fracciones de ejeccion y velocidades de llenado y vaciamiento para cada ventriculo. Ademas se determina el retardo de la contraccion de un ventriculo respecto al otro. El movimiento de paredes se estudia por medio de las imagenes de fase y amplitud, obtenidas al aplicar el aparato matematico de la transformada de Fourier a la ventriculografia nuclear. Estas imagenes diferencian zonas normokineticas de aquinesias e hipoquinesias regionales y permiten identificar segmentos con movimiento paradojico.Los resultados obtenidos con la ventriculografia izquierda y coronariografia en 15 sujetos. Se concluye en la utilidad y valor de la ventriculografia nuclear en una serie de situaciones clinicas

Tecnica de la ventriculografia nuclear. Su valor en cardiopatia isquemica. / Technique of the nuclear ventriculography. Its value in ischeic cardiopathy

Las tecnicas nucleares que emplean camara gamma y computadora digital, han cobrado especial interes en cardiologia durante los ultimos anos.Estos procedimientos presentan como principales ventajas su simplicidad y caracter no invasivo, asi como la informacion que permiten disponer.En el trabajo se presenta la tecnica de ventriculografia nuclear empleada en el laboratorio de los autores y los resultados obtenidos en un grupo de sujetos normales y pacientes con cardiopatia isquemica. Los parametros que se calculan son: fracciones de ejeccion y velocidades de llenado y vaciamiento para cada ventriculo. Ademas se determina el retardo de la contraccion de un ventriculo respecto al otro. El movimiento de paredes se estudia por medio de las imagenes de fase y amplitud, obtenidas al aplicar el aparato matematico de la transformada de Fourier a la ventriculografia nuclear. Estas imagenes diferencian zonas normokineticas de aquinesias e hipoquinesias regionales y permiten identificar segmentos con movimiento paradojico.Los resultados obtenidos con la ventriculografia izquierda y coronariografia en 15 sujetos. Se concluye en la utilidad y valor de la ventriculografia nuclear en una serie de situaciones clinicas

Clonidine and prazosin in the treatment of hypertensive outpatients--a preliminary study.

Clinical assessment of a novel antihypertensive drug combination was undertaken in a group of essential hypertensive patients (n = 20). The effects of several doses of clonidine and its association with prazosin on blood pressure (BP), systolic time intervals (STI), and electrocardiogram (ECG) were investigated. Clonidine monotherapy induced a good BP control at 60%. BP was controlled in those patients in which prazosin was combined with clonidine (87.7%). LVETc was reduced by 0.3, 0.6, and 0.9 mg clonidine daily (p less than 0.05). PEPc was increased by only 0.9 mg, and it was diminished after its combination with 20 mg prazosin daily (p less than 0.05). PEP/LVET index was significantly increased by a higher dose of clonidine (p less than 0.05). ECG intervals did not change with the exception of PR, which was prolonged by 0.9 mg clonidine daily (p less than 0.05). Dry mouth, sedation, constipation, and drowsiness were the main side effects observed during the investigation. These results suggest an alternative treatment of essential hypertension, with a novel clinical application of drugs such as clonidine and prazosin, which have pharmacologic action via different alpha-adrenergic mechanisms.

Hemodynamic effects of atenolol in labile hypertension.

The hemodynamic effects provoked by 15 days treatment with atenolol 100 mg/day in a single oral dose were studied in labile hypertensive patients. Radiocardiography with 131IRHISA was employed in order to calculate: Cardiac output and index (CO, CI); stroke volume and index (SV, SI), total blood volume and index (TBV, TBVI) and total peripheral resistance (TPR). Atenolol caused a significant reduction in arterial pressure, heart rate, CO and CI (p less than 0.001). The drug also reduced TBV (11%) and TBVI (16%) from controls: however, these changes were not significant. A direct relationship was found between CO with heart rate (r = 0.79, p less than 0.01), and between CO with TBV (r = 0.82, p less than 0.01); also an inverse relationship was found between TBV with TPR (r = 0.874, p less than 0.01). These relationships lost significance during treatment with the drug. The lowering of cardiac output contributes to the anti-hypertensive effect of atenolol, but although the reduction in blood volume was not significant it is possible that this also may be a factor.

Hypotensive action of verapamil in a group of hydralazine-dependent hypertensive patients.

Sixteen hydralazine-dependent hypertensive patients (7 females) were included in this clinical study. All patients were being treated with hydralazine, cyclopenthiazide and propranolol in the first visit to the laboratory. Two drugs were maintained during the study: the beta blocker and the diuretic. Hydralazine was discontinued and replaced by placebo during 3 weeks and after this period, verapamil was instituted at increasing doses. Replacing hydralazine by verapamil a better control of hypertension was obtained with a daily dose of 400 mg. The calcium entry blocker causes shortening of PEPc interval probably by reducing afterload which was only observed with the highest dose of verapamil (400 mg). ECG intervals were not modified by the different treatments with the exception of PR which was significantly increased by the major dose of verapamil. The calcium antagonist produced a stable reduction of blood pressure without affecting left ventricular function.

A computerized method of quantitative analysis of ventricular phase distributions.

Phase images from gated equilibrium cardiac studies, were analysed quantitatively by a computerized automatic method. The study included 17 normal subjects and 33 patients with an acute myocardial infarction (AMI). Phase histograms were constructed for each ventricle and their peaks were identified by a convolution algorithm for smoothing and differentiation. Intra- and interventricular phase shifts as well as the percentage of normal contracting pixels (NCP) were calculated. The results showed that the left ventricular ejection fraction (LVEF) tends to decrease when the intraventricular phase shift increases. Interventricular phase shifts out of the normal range (+/- 10 degrees) were observed predominantly in patients with an extensive anterior or anteroseptal AMI. The closest relationship was found between LVEF and the percentage of NCP. This parameter decreases when akinetic and dyskinetic areas increase and could be considered as a quantitative index of the synchronism in myocardial contraction useful in the prognosis and follow-up of patients.

Modification of blood pressure and systolic time intervals by diuretics and beta-blockers in essential hypertension.

Heart rate (HR), blood pressure and systolic time intervals (STI), including total electromechanical systole (QS2), left ventricular ejection time (LVETc), pre-ejection period (PEPc), the PEP/LVET index and the time to the peak of carotid upstroke (Ut), were measured in 24 patients with moderate essential hypertension after 15 days of treatment with oral furosemide (F), hydrochlorothiazide (H), propranolol (P), atenolol (A), furosemide + propranolol (F + P) and hydrochlorothiazide + propranolol (H + P). Except F, all treatments significantly reduced blood pressure; maximal reductions were brought about by A and H + P. The heart rate was most reduced by A. THe QS2c interval was reduced only after F and H, LVETc was significantly reduced by H, A and H + P. Drug combinations prolonged PEPc, while the PEP/LVET index was increased only by H + P. Beta-blockers significantly prolonged the Ut. It is concluded that diuretics shorten QS2c mainly through reduction in blood volume. The H + P combination diminishes contractility and cardiac output and should not be employed in heart failure.