Impact of inhaled nitric oxide on platelet aggregation and fibrinolysis in rats with endotoxic lung injury. Role of cyclic guanosine 5'-monophosphate

As inhaled nitric oxide (iNO) may differently increase bleeding time (BT) and inhibit platelet aggregation in normal and lung-injured patients or experimental models, we studied the effects of iNO on hemostasis in presence and absence of an endotoxic lung injury in the rat. Eight hours after intratracheal administration of endotoxin (lipopolysaccharide [LPS]) or its solvent (phosphate-buffered solution [PBS]), four groups of rats were randomized according to the presence or absence of 15 ppm iNO added for an additional 10 h. We measured BT, ex vivo platelet aggregation, plasma fibrinogen, euglobulin clot lysis time (ECLT), and platelet and aortic cyclic guanosine 5'-monophosphate (cGMP) contents. Acute lung inflammation did not influence BT, but increased platelet aggregability, fibrinogen levels, and platelet and aortic cGMP. In control and endotoxic rats, iNO increased BT, reduced platelet aggregability, and increased platelet cGMP. iNO increased aortic cGMP only in healthy rats. ECLT was increased by LPS and unchanged with iNO. These results suggest that the extrapulmonary "systemic" effects induced by iNO on hemostasis were not strictly similar in healthy and LPS rats, inflammation inducing proper changes in coagulation parameters. However, iNO attenuated the procoagulant activity induced by acute lung inflammation, suggesting a potentially beneficial effect of this therapy.     

Right and left ventricular geometry and myocyte contractile processes with dilated cardiomyopathy: myocyte growth and beta-adrenergic responsiveness

OBJECTIVES: Comparison of the effects of supraventricular tachycardia-induced dilated cardiomyopathy on left and right ventricular isolated myocyte geometry and function. BACKGROUND: Chronic ventricular tachycardia and supraventricular tachycardia cause left ventricular dilation and dysfunction in humans. However, it is unknown whether supraventricular tachycardia-induced dilated cardiomyopathy is a homogenous process for both the left and right ventricles. METHODS: Dilated cardiomyopathy was induced by rapid atrial pacing (240 beats/min, 3 weeks) in 5 pigs. Five age- and weight-matched pigs served as controls. Ventricular mass was measured, myocyte dimensions were obtained, and isolated right and left ventricular myocyte contractile performance was evaluated at baseline and after beta-adrenergic receptor stimulation. RESULTS: With the development of dilated cardiomyopathy, there was no change in left ventricular mass. In contrast, right ventricular mass was increased, as was right ventricular myocyte cross-sectional area. In the control group, baseline right ventricular myocyte contractile function was increased compared to left ventricular myocytes. beta-adrenergic receptor stimulation increased myocyte contractile function in both left and right ventricular myocytes. With supraventricular tachycardia-induced cardiomyopathy, both left and right ventricular myocyte contractile function and beta-adrenergic responsiveness were reduced. CONCLUSIONS: This study demonstrated differences in left and right ventricular myocyte growth with supraventricular tachycardia-induced dilated cardiomyopathy and this differential growth response was associated with changes in contractile performance. Thus, in this model of cardiomyopathic disease, left and right ventricular growth and changes in contractile performance are not a homogenous process.     

Clinical and hemodynamic follow-up of left ventricular to aortic conduits in patients with aortic stenosis

To assess the long-term results of left ventricular outflow tract reconstruction utilizing an apical left ventricular to aortic valved (porcine) conduit the clinical and hemodynamic data were reviewed from 24 patients who had placement of an apico-aortic conduit. Eighteen of the patients are asymptomatic and taking no cardiac medications. Three patients were reoperated on, one patient 1.5 years after his original operation for subacute bacterial endocarditis and two patients 3 to 4 years after their original operation for severe conduit valve insufficiency. None of the patients is taking anticoagulants and no thromboembolic events have occurred. Postoperative catheterization has been performed 1 to 1.5 years (mean 1.2) after repair in 15 of 21 patients. The rest left ventricular outflow tract gradient has decreased from 102.5 +/- 20 mm Hg preoperatively to 14.8 +/- 9.9 mm Hg postoperatively (probability [p] less than 0.001). Some degree of conduit obstruction was demonstrated by catheter passage in 11 of the 15 patients. In these 11 patients, the obstruction occurred at three distant sites: at the egress of the left ventricle in 9, at the porcine valve in 5 and at the aortic to conduit junction in 1. Isometric exercise in five and supine bicycle exercise in six patients increased the left ventricular outflow tract gradient by 2.5 +/- 1.1 and 20.8 +/- 11.8 mm Hg, respectively, despite an increase in cardiac index of 1 +/- 0.3 and 3.7 +/- 0.4 liters/min per m2, respectively. The data suggest that a left ventricular to aortic conduit is an effective form of therapy for severe left ventricular outflow tract obstruction.     

Diminished contractile reserve in patients with left ventricular hypertrophy and increased end-systolic stress during Dobutamine stress echocardiography

Left ventricular hypertrophy (LVH) is associated with decreased contractile response to inotropic stimulation in animal models, but this has not been documented in humans. To determine whether LVH is associated with decreased myocardial contractile reserve, we measured left ventricular mass, heart rate-corrected velocity of circumferential fiber shortening (Vcfc), end-systolic stress, and LV ejection fraction (LVEF) in patients with LVH and increased end-systolic stress (n = 6) and in patients without LVH (n = 7) who had a normal response to dobutamine stress echocardiography (increased LVEF and no wall motion abnormalities). The afterload-dependent indexes of left ventricular systolic performance were normal at baseline and showed significant increases at peak dobutamine dose (LVH group: Vcfc 0.91 +/- 0.11 to 1.76 +/- 0.59, p = 0.006; LVEF 49 +/- 5 to 65 +/- 6, p = 0.001; group without LVH: Vcfc 1.16 +/- 0.24 to 1.99 +/- 0.36, p = 0.001; LVEF 61 +/- 6 to 68 +/- 6, p = 0.05). The Vcfc/ end-systolic stress relation, a load-independent index of myocardial contractility, rose in a dose-dependent fashion in both groups, but the increment was significantly less for patients with LVH (p < 0.02), suggesting a blunted myocardial contractile reserve to inotropic stimulation. The change in heart rate-corrected velocity of circumferential fiber shortening per unit of change in end-systolic stress in each patient at each dobutamine dose showed a linear and inverse relationship. The increment in heart rate-corrected velocity of circumferential fiber shortening for a given reduction in end-systolic stress was larger in patients without LVH than in patients with LVH (p = 0.01). These results suggest that in patients with LVH and increased end-systolic stress, ventricular performance is maintained at the expense of limited myocardial contractile reserve, and that inotropic stimulation unmasks this abnormality, despite a normal response in LVEF and velocity of circumferential fiber shortening. This approach may identify patients with LVH at risk of developing systolic dysfunction and heart failure.     

Dissociation of left ventricular hypertrophy, beta-myosin heavy chain gene expression, and myosin isoform switch in rats after ascending aortic stenosis

The regulation of angiotensin II (Ang II) receptors and Ang II-induced modulation of intracellular Ca2+ concentration in cardiac cells from hearts of experimentally induced hypertensive deoxycorticosterone acetate (DOCA)-salt and control unilaterally nephrectomized (Uni-Nx) Sprague-Dawley rats was assessed. Ang II receptor density and intracellular Ca2+ concentration measurements were examined in adult ventricular myocytes and fibroblasts by radioligand binding assay and digital imaging using fura 2 methodology, respectively. Four-week DOCA-salt treatment induced hypertension associated with cardiac hypertrophy. Ang II binding studies demonstrated that adult ventricular myocytes and fibroblasts possess mainly the AT1 subtype receptor. Moreover, DOCA-salt hypertension was associated with a 1.8-fold increase in Ang II-specific binding compared with myocytes from Uni-Nx control rats. Intracellular Ca2+ responses induced by increasing Ang II concentrations (10[-12] to 10[-4] mol/L) were significantly enhanced in cardiomyocytes from DOCA-salt rats. The effects of Ang II on intracellular Ca2+ spike frequency were unaltered in cardiomyocytes from DOCA-salt-hypertensive rats. The density of AT1 subtype receptors was not modified in ventricular fibroblasts after DOCA-salt treatment. Ang II increased intracellular Ca2+ concentration similarly in ventricular fibroblasts from normal and hypertensive rats. In conclusion, DOCA-salt hypertension is characterized by an increased AT1 receptor density and intracellular calcium responses in ventricular myocytes, whereas in ventricular fibroblasts the AT1 receptor status is unaltered. These findings report for the first time the cardiac cell-specific implication of Ang II and the intracellular calcium signaling pathway stimulated by the AT1 receptor in cardiac hypertrophy in DOCA-salt-hypertensive rats.     

Long-term effects of delapril hydrochloride on procollagen type III amino-terminal peptide, left ventricular mass and left ventricular function in hypertensive patients

The long-term effect of delapril hydrochloride, a non-sulfhydryl angiotensin converting enzyme inhibitor, on serum concentrations of procollagen type III amino-terminal peptide (PIIIP) and left ventricular mass (LVM) and function were investigated in 15 hypertensive patients. Patients were treated with delapril hydrochloride 30 mg/day po for 12 months. Blood samples and an echocardiogram were obtained before treatment and after 6 and 12 months of treatment. Blood pressure, PIIIP, and LVM significantly decreased associated with an increase in left ventricular fractional shortening and mean systolic and diastolic posterior wall velocity at 6 and 12 months of treatment. Positive correlations between PIIIP and LVM (r=0.49, p<0.005) and negative correlations between PIIIP and left ventricular fractional shortening (r=-0.31, p<0.05) were found. Delapril hydrochloride reduced PIIIP and LVM and improved cardiac function in hypertensive patients.     

The subtype-2 (AT2) angiotensin receptor regulates renal cyclic guanosine 3', 5'-monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats

The renal effects of angiotensin II(AII) are attributed to AT1 receptors. In contrast, the function of renal AT2 receptors in unknown. Using a microdialysis technique, we monitored changes in renal interstitial fluid (RIF) prostaglandin E2 (PGE2) and cyclic guanosine 3', 5'-monophosphate (cGMP) in response to dietary sodium (Na) depletion alone, or Na depletion or normal Na diet combined with the AT1 receptor blocker, Losartan, the AT2 receptor blocker, PD 123319 (PD), or angiotensin II, individually or combined in conscious rats. Na depletion significantly increased PGE2 and cGMP. During Na depletion, Losartan decreased PGE2 and did not change cGMP. In contrast, PD significantly increased PGE2 and decreased cGMP. Combined administration of Losartan and PD decreased PGE2 and cGMP. During normal Na diet, RIF PGE2 and cGMP increased in response to angiotensin II. Neither Losartan nor PD, individually or combined, changed RIF PGE2 or cGMP. Combined administration of angiotensin II and Losartan or PD produced a significant decrease in response of PGE2 and cGMP to angiotensin II, respectively. These data demonstrate that activation of the reninangiotensin system during Na depletion increases renal interstitial PGE2 and cGMP. The AT1 receptor mediates renal production of PGE2. The AT2 receptor mediates cGMP. AT2 blockade potentiates angiotensin-induced PGE2 production at the AT1 receptor.     

Sudden cardiac death in patients with arterial hypertension and left ventricular hypertrophy on antihypertensive therapy

The hypertrophy of the left ventricle in patients with arterial hypertension is an independent risk factor which increases c 9 times the probability of sudden cardiac death. Despite the fact that the incidence of sudden cardiac death in patients with arterial hypertension is low, regarding the high occurrence of hypertension it represents a significant medical problem. The therapy of arterial hypertension is able to decrease the general and cardiovascular mortalities with significant interspecies characteristics of individual antihypertensive drugs, as well as to promote the regression of hypertrophy of the left ventricle. The therapy per se can however increase the risk of cardiovascular complications: until now the complication of the therapy by diuretics rich in potassium and beta-blockers are best distinguished. Calcium antagonists are effective antihypertensive drugs but they do not decrease the total mortality. ACE inhibitors have a marked antihypertensive effect and few adverse effects, but until now there is not a sufficient number of large prospective studies which would definitely confirm the preliminary promising findings. Despite the presented problems the cured patients with arterial hypertension have a substantially better prognosis than patients that are not being cured.     

Angiotensin-converting enzyme inhibition and angiotensin II subtype-1 receptor blockade during the progression of left ventricular dysfunction: differential effects on myocyte contractile processes

Inhibition of the angiotensin-converting enzyme (ACE) in the setting of chronic left ventricular (LV) dysfunction has been demonstrated to have beneficial effects on survival and symptoms. However, whether ACE inhibition has direct effects on myocyte contractile processes and if these effects are mediated primarily through the AT1 angiotensin-II receptor subtype remains unclear. The present project examined the relationship between changes in LV and myocyte function and beta adrenergic receptor transduction in four groups of six dogs each: (1) Rapid Pace: LV failure induced by chronic rapid pacing (4 weeks; 216 +/- 2 bpm); (2) Rapid Pace/ACEI: concomitant ACE inhibition (ACEI: fosinopril 30 mg/kg b.i.d.) with chronic pacing; (3) Rapid Pace/AT1 Block: concomitant AT1 Ang-II receptor blockade [Irbesartan: SR 47436(BMS-186295) 30 mg/kg b.i.d.] with chronic pacing; and (4) Control: sham controls. With Rapid Pace, the LV end-diastolic volume increased by 62% and the ejection fraction decreased by 53% from control. With Rapid Pace/ACEI, the LV end-diastolic volume was reduced by 24% and the ejection fraction increased by 26% from Rapid Pace only values. Rapid Pace/AT1 Block did not improve LV geometry or function from Rapid Pace values. Myocyte contractile function decreased by 40% with Rapid Pace and increased from this value by 32% with Rapid Pace/ACEI. Rapid Pace/AT1 Block had no effect on myocyte function when compared with Rapid Pace values. With Rapid Pace/ACEI, beta receptor density and cyclic AMP production were normalized and associated with an improvement in myocyte beta adrenergic response compared with Rapid Pace only. Although Rapid Pace/AT1 also normalized beta receptor density, cyclic AMP production was unchanged and myocyte beta adrenergic response was reduced by 15% compared with Rapid Pace only. ACE inhibition with chronic rapid pacing improved LV and myocyte geometry and function, and normalized beta receptor density and cyclic AMP production. However, AT1 Ang-II receptor blockade with chronic rapid pacing failed to provide similar protective effects on LV and myocyte geometry and function. These unique findings suggest that the effects of ACE inhibition on LV geometry and myocyte contractile processes in the setting of developing LV failure are not primarily caused by modulation of AT1 Ang-II receptor activation.     

Combined effects of blood pressure and body mass index on left ventricular structure in middle-aged males: cross-sectional and 2-year longitudinal results

OBJECTIVE: To compare the 2-year longitudinal with the cross-sectional relationships of blood pressure and body mass index with echocardiographic left ventricular measurements in middle-aged males with no history of cardiovascular disease or hypertension. METHODS: M-mode echocardiograms of adequate quality were obtained at initial and 2-year follow-up examinations in 177 subjects. Measurements of left ventricular wall thickness and internal dimensions were made, and estimates of left ventricular mass/height were calculated. Longitudinal changes in left ventricular measurements and risk factors were computed as the differences between the follow-up and initial values. RESULTS: Systolic blood pressure (SBP) was significantly associated with left ventricular mass/height and wall thickness in cross-sectional and in longitudinal analyses. Similar results were observed after adjusting for age, body mass index, sport activity and heart rate. Although body mass index was strongly related to left ventricular mass/height, wall thickness and internal dimension in the cross-sectional study, no significant associations were observed between changes in body mass index and in left ventricular measurements. CONCLUSIONS: The present study emphasizes the differential effects of spontaneous changes in blood pressure and body mass index on the evolution of the left ventricular mass in middle-aged males. Spontaneous changes in SBP during the 2-year follow-up period were associated with rapid changes in left ventricular structure. The 2-year period might not have been sufficient for body mass index to induce changes in left ventricular structure. The duration and amplitude of body weight changes which entail changes in left ventricular mass remain to be determined by further longitudinal investigations.     

Late thrombolysis in acute myocardial infarct: short and long term effects on left ventricular function

Although the efficacy of intravenous thrombolysis in the treatment of acute myocardial infarction has been widely proved, some uncertainty concerning the "temporal window" of administration still persists. The aim of the present investigation was to study whether the late administration of a thrombolytic agent (6 or more hours after the onset of symptoms of acute myocardial infarction) offers any short or long-term advantages with regards to left ventricular function and clinical outcome. We studied 100 consecutive patients at their first episode of myocardial infarction, admitted to Coronary Unit within 24 hours of the onset of symptoms. Of these patients, 62 were administered rt-PA (44 patients within the 6th hour, and 18 between the 6th and 24th hour after the onset of symptoms) and the 38 remaining patients, who did not receive the thrombolytic agent (due to concerns with respect to possible complications), constituted the control group (18 admitted within 6 hours and 20 between 6 and 24 hours). All patients underwent serial electrocardiograms, and echocardiograms upon admission and at discharge to assess the ejection fraction, the asynergy score and the percentage of ischemic area. Furthermore, the survivors were invited for a follow-up examination one year after their acute initial episode. Seven cases of heart failure occurred, before discharge, among the control patients admitted 6 to 24 hours after onset of symptoms, compared with no cases in the subgroup of patients treated with rt-PA during the same time period (p = 0.0068).(ABSTRACT TRUNCATED AT 250 WORDS)     

Noninvasive assessment of the direct action of oral nifedipine and nicardipine on left ventricular contractile state in patients with systemic hypertension: importance of reflex sympathetic responses

BACKGROUND: Alveolar macrophages from patients with sarcoidosis were analyzed for their ability to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1-beta), and interleukin-6 (IL-6). RESULTS: Constitutive release of all three monokines in these patients was concomitantly increased in the active state of disease in comparison with inactive sarcoidosis or healthy control subjects. Alveolar macrophages from patients with inactive sarcoidosis compared with cells from healthy subjects showed increased spontaneous secretion of TNF-alpha and IL-6 only, whereas the constitutive release of IL-1-beta was similar as in healthy volunteers. In vitro stimulation of alveolar macrophages from healthy control subjects with lipopolysaccharide or pokeweed mitogen led to a time- and dose-dependent enhanced secretion of TNF-alpha, IL-1-beta, and IL-6. In a similar manner, with corresponding cells from patients with sarcoidosis the secretion of all three cytokines could be further increased by stimulation with lipopolysaccharide or pokeweed mitogen. CONCLUSIONS: The data presented indicate that an increased release of TNF-alpha, IL-1-beta, and IL-6 correlates to disease activity and may play a critical part in the pathogenesis of sarcoidosis.     

Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart

BACKGROUND: The basic pharmacology of the third-generation beta-blocking agent carvedilol differs considerably from second-generation compounds such as metoprolol. Moreover, carvedilol may produce different, ie, more favorable, clinical effects in chronic heart failure. For these reasons, we compared the effects of carvedilol and metoprolol on adrenergic activity, receptor expression, degree of clinical beta-blockade, hemodynamics, and left ventricular function in patients with mild or moderate chronic heart failure. METHODS AND RESULTS: The effects of carvedilol versus metoprolol were compared in two concurrent placebo-controlled trials with carvedilol or metoprolol that had common substudies focused on adrenergic, hemodynamic, and left ventricular functional measurements. All subjects in the substudies had chronic heart failure resulting from idiopathic dilated cardiomyopathy. Carvedilol at 50 to 100 mg/d produced reductions in exercise heart rate that were similar to metoprolol at 125 to 150 mg/d, indicating comparable degrees of beta-blockade. Compared with metoprolol, carvedilol was associated with greater improvement in New York Heart Association functional class. Although there were no significant differences in hemodynamic effects between the carvedilol and metoprolol active-treatment groups, carvedilol tended to produce relatively greater improvements in left ventricular ejection fraction, stroke volume, and stroke work compared with changes in the respective placebo groups. Carvedilol selectively lowered coronary sinus norepinephrine levels, an index of cardiac adrenergic activity, whereas metoprolol did not lower coronary sinus norepinephrine and actually increased central venous norepinephrine levels. Finally, metoprolol was associated with an increase in cardiac beta-receptor density, whereas carvedilol did not change cardiac beta-receptor expression. CONCLUSIONS: The third-generation beta-blocking agent carvedilol has substantially different effects on left ventricular function, hemodynamics, adrenergic activity, and beta-receptor expression than dose the second-generation compound metoprolol. Some or all of these differences may explain the apparent differences in clinical results between the two compounds.     

Blood pressure and left ventricular mass in children with different maternal histories of hypertension: the Hypertension in Pregnancy Offspring Study

The treatment of chronic, nonhealing wounds is discussed. The authors have successfully utilized locally acting growth factors as an adjunct to aggressive, comprehensive management in a clinical setting. At the Holmes Regional Wound Care Center, wounds with an average duration of 75 weeks at presentation were 100% epithelialized in an average of 10 weeks of therapy. The use of topical PROCUREN, or autologous platelet-derived wound healing factors (PDWHF) is introduced to the podiatric literature.     

Intrapericardial delivery of L-arginine reduces the increased severity of ventricular arrhythmias during sympathetic stimulation in dogs with acute coronary occlusion: nitric oxide modulates sympathetic effects on ventricular electrophysiological properties

BACKGROUND: Nitric oxide (NO) modulates autonomic effects on myocardial contractility and sinus and atrioventricular nodal function of the heart. Whether NO influences autonomic actions on ventricular electrophysiological properties and arrhythmogenesis is not known. METHODS AND RESULTS: Four groups consisting of 43 autonomically denervated dogs were studied. To "superfuse" sympathetic nerves innervating the ventricles, test drugs were introduced into the pericardial sac for 30 minutes, and their effects on ventricular effective refractory period (ERP) and arrhythmia development were assessed before and during sympathetic stimulation (SS). In group 1 (n=12), ventricular ERPs showed no significant difference between control and superfusion with L-arginine, a NO precursor (222+/-20 versus 222+/-19 ms, P=.485). However, L-arginine significantly reduced SS-induced ERP shortening compared with control (9+/-7 versus 13+/-7 ms, P<.001). Simultaneous administration of N(G)-monomethyl-L-arginine (2 mg/mL) abolished the inhibitory effects of L-arginine (13+/-7 versus 13+/-7 ms, P=.885). In group 2 (n=15), the severity of ventricular arrhythmias significantly increased during SS. L-Arginine reduced this increase caused by SS. In group 3 (n=8), plasma norepinephrine spillover measured from the coronary sinus significantly increased during SS and was reduced by pericardial superfusion with L-arginine compared with control (6005.2+/-1525.6 versus 8503.4+/-2044.5 pg/min, P=.012). In group 4 (n=8), L-arginine pericardial superfusion significantly increased NO overflow measured from the coronary sinus during SS (93.25+/-59.20 versus 114.82+/-74.92 nmol/min, P=.043). CONCLUSIONS: Pericardial L-arginine reduces ERP shortening and increased severity of ischemic ventricular arrhythmias during SS in dogs. NO-induced reduction of norepinephrine release in the heart may be one of the underlying mechanisms.     

Effects of continuous alendronate treatment on bone mass and mechanical properties in ovariectomized rats: comparison with pamidronate and etidronate in growing rats

Providencia stuartii contains a chromosomal 2'-N-acetyltransferase [AAC(2')-Ia] involved in the O acetylation of peptidoglycan. The AAC(2')-Ia enzyme is also capable of acetylating and inactivating certain aminoglycosides and confers high-level resistance to these antibiotics when overexpressed. We report the identification of a locus in P. stuartii, designated aarF, that is required for the expression of AAC(2')-Ia. Northern (RNA) analysis demonstrated that aac(2')-Ia mRNA levels were dramatically decreased in a P. stuartii strain carrying an aarF::Cm disruption. The aarF::Cm disruption also resulted in a deficiency in the respiratory cofactor ubiquinone. The aarF locus encoded a protein that had a predicted molecular mass of 62,559 Da and that exhibited extensive amino acid similarity to the products of two adjacent open reading frames of unknown function (YigQ and YigR), located at 86 min on the Escherichia coli chromosome. An E. coli yigR::Kan mutant was also deficient in ubiquinone content. Complementation studies demonstrated that the aarF and the E. coli yigQR loci were functionally equivalent. The aarF or yigQR genes were unable to complement ubiD and ubiE mutations that are also present at 86 min on the E. coli chromosome. This result indicates that aarF (yigQR) represents a novel locus for ubiquinone production and reveals a previously unreported connection between ubiquinone biosynthesis and the regulation of gene expression.     

Short-term effects of captopril on exercise tolerance in patients with chronic stable angina pectoris and normal left ventricular function

A double-blind, placebo-controlled, crossover study was carried out to evaluate the short-term effects of captopril on exercise tolerance in 18 normotensive patients with chronic stable angina pectoris and normal left ventricular function. Captopril 25 mg (or placebo) was given twice, i.e. in the evening (10 p.m.) and the following morning (8 a.m.), prior to a maximal symptom-limited bicycle exercise test (11 a.m.). Captopril reduced the systolic and diastolic blood pressures at rest (p < 0.01) without causing any reflex tachycardia. The time to onset of S-T depression was prolonged (p < 0.05), and the maximal S-T depression was reduced (p < 0.02). No differences were found between captopril and placebo in total exercise duration or time to onset of angina. The effects of captopril on exercise-induced ischemia were demonstrated most clearly in patients who responded with a greater than 10 mm Hg fall in the resting systolic blood pressure. In conclusion, this study suggests that captopril has anti-ischemic properties, which may be of importance in the treatment of patients with chronic stable angina and normal left ventricular function. These beneficial effects probably relate to a reduction in afterload and myocardial wall stress and therefore a reduction in myocardial oxygen demand.     

Clinical study on combined treatment of shuizhi tuyuan powder and nifedipine in treating hypertension patients complicated with left ventricular hypertrophy

Patients with essential hypertension complicated with left ventricular hypertrophy (LVH) confirmed by ultrasonic cardiography were divided randomly into observation group and control group. Both groups were treated with nifedipine. Shuizhi Tuyuan Powder (SZTYP, consisted of Hirudo nipponia and Eupolyphaga sinensis) was given in addition to the observation group. The therapeutic course for the two groups were 6 months. Results showed that after one course of treatment, the myocardial weight index lowered from 136.8 +/- 7.5 g/m2 to 130.5 +/- 6.4 g/m2 in observation group, while in control group, it lowered from 136.7 +/- 7.4 g/m2 to 134.3 +/- 6.2 g/m2, the difference between the two groups was significant (P < 0.01). The symptoms were relieved in part of the patients with early stage of cerebrovascular disease treated with SZTYP. The results suggested that SZTYP combined with nifedipine has active curative effect on essential hypertension patients complicated by LVH and part patients in early stage of cerebrovascular disease.     

Long-term (5 year) effects of transient (silent) ischaemia on left ventricular systolic function in stable angina. Clinical and radionuclide study

AIMS: (a) to assess short (1 year) and long-term (5 year) changes in left ventricular ejection fraction in patients with stable coronary disease with or without ECG evidence of transient ischaemia during daily life on routine therapy, and (b) to assess whether patients with recurrent transient ischaemic episodes have a particular propensity to gradual deterioration in left ventricular ejection fraction in the absence of infarction. METHODS AND RESULTS: One hundred and forty eight patients (127 males; mean age 59 years), part of a natural history cohort of 172 patients who had undergone exercise testing, 48 h ambulatory ST monitoring, and resting radionuclide ventriculography at baseline, and who had not suffered any intervening cardiac event, underwent repeat radionuclide ventriculography at 1 year follow-up on identical or very similar medications. Furthermore, 56 patients (50 males; mean age 65 years) of this cohort, who had ischaemia both on exercise testing and ambulatory monitoring at baseline (n=33), or no ischaemia on either test at baseline (n=23), and who had suffered no intervening event, underwent repeat exercise testing, ambulatory monitoring and radionuclide ventriculography at a mean of 61.8 months follow-up. In 38 of these 56 cases, long-term testing mirrored baseline testing in terms of presence or absence of ischaemia (both tests +, n=25; both tests -, n=13). At one year there was no change in left ventricular ejection fraction, either for the whole group (n=148; left ventricular ejection fraction 47=11.6% - 47.13+11.07%, P=ns) or for subgroups with (n=62; left ventricular ejection fraction 48+12.1%-48.5+10.5%, P=ns) and without (n=86; left ventricular ejection fraction 46.2+10.4%-46.2+11.3%, P=ns) evidence of transient ischaemia at baseline. At 61 months, there was a small fall in mean left ventricular ejection fraction for the total study group (n=56; left ventricular ejection fraction 45.8+9.3%-42.1+8.8%, P<0.05); however, this fall was not significant for those patients with both baseline and 5 year evidence of transient ischaemia (n=25; left ventricular ejection fraction 44.9+8.7%-41.3+7.5%, P=0.056). CONCLUSION: In medically treated stable coronary patients who do not suffer any intervening cardiac event, recurrent transient (silent) ischaemic episodes do not, in themselves, lead to gradual deterioration in left ventricular systolic function over a 1-5 year period.