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Background Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). Objectives This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. Methods The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life–5 Dimensions–5 Level visual analogue scale at 12 weeks. Results MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). Conclusions Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408)., Central Illustration

Aims: The prevalence of premature coronary artery disease (CAD) in India is two to three times more than other ethnic groups. Untreated heterozygous familial hypercholesterolemia (FH) is one of the important causes for premature CAD. As the age advances, these patients without treatment have 100 times increased risk of cardiovascular (CV) mortality resulting from myocardial infarction (MI). Recent evidence suggests that one in 250 individuals may be affected by FH (nearly 40 million people globally). It is indicated that the true global prevalence of FH is underestimated. The true prevalence of FH in India remains unknown. Methods: A total of 635 patients with premature CAD were assessed for FH using the Dutch Lipid Clinical Network (DLCN) criteria. Based on scores, patients were diagnosed as definite, probable, possible, or no FH. Other CV risk factors known to cause CAD such as smoking, diabetes mellitus, and hypertension were also recorded. Results: Of total 635 patients, 25 (4%) were diagnosed as definite, 70 (11%) as probable, 238 (37%) as possible, and 302 (48%) without FH, suggesting the prevalence of potential (definite + probable) FH of about 15% in the North Indian population. FH is more common in younger patients, and they have lesser incidence of common CV risk factors such as diabetes, hypertension, and smoking than the younger MI patients without FH (26.32% vs.42.59%; 17.89% vs.29.44%; 22.11% vs.40.74%). Conclusion: FH prevalence is high among patients with premature CAD admitted to a cardiac unit. To detect patients with FH, routine screening with simple criteria such as family history of premature CAD combined with hypercholesterolemia, and a DLCN criteria score >5 may be effectively used. Keywords: Familial hypercholesterolemia, Premature coronary artery disease, Dutch Lipid Clinic Network Criteria, Correction factor, Arcus cornealis

Objective: Primary objective was to compare the effects of atorvastatin 40 mg vs 80 mg on LDL-C in Indian patients with atherosclerotic dyslipidemia. Secondary objectives were to compare the effects of atorvastatin 40 mg vs 80 mg on HDL-C and triglycerides and also comparing of side effects (myopathy, hepatotoxicity and new onset diabetes mellitus) of both doses. Method: This Study is A Prospective, randomized, open-label, comparative study. This study was conducted on 240 patients of dyslipidemia (as per ACC/AHA 2013 lipid guidelines) attending the OPD/wards/CCU of department of cardiology, Sir Ganga Ram Hospital. They were randomly divided into 2 groups of 120 each. Group A consisted patients who received Atorvastatin 40 mg daily and Group B Atorvastatin 80 mg daily. The follow up period was 6 months. Results: At 3 and 6 month follow up, Atorvastatin 40 mg leads to mean LDL cholesterol reduction of 47.18 ± 20.81 & 50.03 ± 18.06 respectively. While Atorvastatin 80 mg results in LDL reduction as 50.11 ± 15.85 & 52.30 ± 13.72. The comparison between two doses revealed a non-significant difference (p = .118 & p = .149 respectively).At 6 months of follow up, few patients reported myalgia (2 in group A and 7 in Group B). The difference between groups was significant (p = .045). Although none of our patient had significant elevation of CPK. Conclusion: This study concluded that both doses of atorvastatin (40 & 80 mg) are equally efficacious in improving dyslipidemia but higher dose leads to more incidence of myalgia. Keywords: Atherosclerosis, Atorvastatin, Dyslipidemia, Myalgia

Cardiac rehabilitation (CR) after myocardial infarction is highly effective. It is unavailable in public hospitals in India due to limited resources. Our objective was to develop a scalable model of CR for India based on yoga, which could also appeal to some groups with low uptake of CR (e.g., ethnic minorities, women, and older people) globally. The intervention was developed using a structured process. A literature review and consultations with yoga experts, CR experts, and postmyocardial infarction patients were conducted to systematically identify and shortlist appropriate yoga exercises and postures, breathing exercises, meditation and relaxation practices, and lifestyle changes, which were incorporated into a conventional CR framework. The draft intervention was further refined based on the feedback from an internal stakeholder group and an external panel of international experts, before being piloted with yoga instructors and patients with myocardial infarction. A four-phase yoga-based CR (Yoga-CaRe) programme was developed for delivery by a single yoga instructor with basic training. The programme consists of a total of 13 instructor-led sessions (2 individual and 11 group) over a 3-month period. Group sessions include guided practice of yoga exercises and postures, breathing exercises, and meditation and relaxation practices, and support for the lifestyle change and coping through a moderated discussion. Patients are encouraged to self-practice daily at home and continue long-term with the help of a booklet and digital video disc (DVD). Family members/carers are encouraged to join throughout. In conclusion, a novel yoga-based CR programme has been developed, which promises to provide a scalable CR solution for India and an alternative choice for CR globally. It is currently being evaluated in a large multicentre randomised controlled trial across India.

Background Cardiac rehabilitation (CR) is a standard treatment for secondary prevention of acute myocardial infarction (AMI) in high income countries (HICs), but it is inaccessible to most patients in India due to high costs and skills required for multidisciplinary CR teams. We developed a low-cost and scalable CR program based on culturally-acceptable practice of yoga (Yoga-CaRe). In this paper, we report the rationale and design for evaluation of its effectiveness and cost-effectiveness. Methods This is a multi-center, single-blind, two-arm parallel-group randomized controlled trial across 22 cardiac care hospitals in India. Four thousand patients aged 18–80 years with AMI will be recruited and randomized 1:1 to receive Yoga-CaRe program (13 sessions supervised by an instructor and encouragement to self-practice daily) or enhanced standard care (3 sessions of health education) delivered over a period of three months. Participants will be followed 3-monthly till the end of the trial. The co-primary outcomes are a) time to occurrence of first cardiovascular event (composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke and emergency cardiovascular hospitalization), and b) quality of life (Euro-QoL-5L) at 12 weeks. Secondary outcomes include need for revascularization procedures, return to pre-infarct activities, tobacco cessation, medication adherence, and cost-effectiveness of the intervention. Conclusion This trial will alone contribute >20% participants to existing meta-analyses of randomized trials of CR worldwide. If Yoga-CaRe is found to be effective, it has the potential to save millions of lives and transform care of AMI patients in India and other low and middle income country settings.

Diabetes mellitus (DM) is a known independent predictor of mortality following acute myocardial infarction (AMI). In addition, patients with DM may have other risk factors for AMI such as hypertension (HTN), tobacco use, physical inactivity. This study aimed to explore the distribution of cardiovascular (CV) risk factors among patients of AMI with and without DM. Yoga-CaRe, a multicenter randomized controlled trial, included patients of AMI (first or consequent AMI) with DM (n=856) and without DM (n=2330), aged 18-80 years from 24 cardiac centers across India. The baseline socio-demographics, clinical and behavioral characteristics of those with and without DM were analyzed using multivariable logistic/linear regression models, sequentially adjusted for age, gender, education and physical inactivity. Patients of AMI with DM were older as compared to those without DM (mean age 56.4± 9.4 vs. 51.9 ± 11.2). Patients with DM had higher odds of having hypertension, being physically inactive and had lower odds of self-reported ever tobacco use. Patients with DM had higher mean waist circumference, systolic and diastolic blood pressure (Table). No differences were found in body mass index between diabetes and nondiabetes groups.The observed differential distribution of CV risk factors in AMI patients with DM calls for a tailored rehabilitation plan. Cardiovascular risk factors among AMI patients with diabetes vs. without diabetesVariableDiabetes (n=856)Without diabetes (n=2330)Adjusted OR/Regression coefficient* [95% CI]Ever tobacco use (%)34.2%49.2%0.73 [0.60-0.88]Physical inactivity (%)57.8%49.2%1.38 [1.18-1.62]Body Mass Index ≥25Kg/m2 (%)57.6%50.8%1.13 [0.95-1.34]Waist circumference (cm) (mean)99.3±20.792.3±17.94.7 [3.1-6.3]*Systolic blood pressure (mmHg) (mean)123.4±17.2118.8±16.13.6 [2.3-4.9]*Diastolic blood pressure (mmHg) (mean)76.7±10.774.9±10.31.9 [1.02-2.7] *Hypertension (%)53.1%18.6%3.8 [2.9-5.1] Disclosure D. Soni: None. C.M. Ambalam: None. V.S. Ajay: None. K. Singh: None. K. Singh: None. P.A. Praveen: None. A. Roy: None. S.C. Manchanda: None. B. Mohan: None. P.C. Negi: None. P. Bhat: None. K.S. Sadananda: None. P.M. R.: None. P. Sarma: None. S. Natarajan: None. C. Narasimhan: None. N. Desai: None. S. Patil: None. D.S. Chadha: None. S. Chandra: None. S. Kinra: None. D. Prabhakaran: None.

Hypertension is a major public health problem and is an impor tant risk factor for stroke, coronary heart disease and renal failure. The blood pressure is not well controlled with drug therapy in large number of individuals, especially in the developing countries. There is a need for less expensive nonpharmacological alternative methods to control blood pressure. Yoga may be such cost-effective alternative. Several uncon trolled and ran do mized control trials have evaluated short- and long-term effects of yoga/meditation-based techniques in prehypertension and mild hypertension. Though, the results are mixed and there are several methodological limitations in reported studies, majority of studies demonstrate a modest decrease in both systolic and diastolic blood pressure. This modest decrease may significantly decrease the stroke mortality and coronary heart disease in general population. A recent scientific statement of American Heart Association also suggests that it is reasonable for all individuals with blood pressure levels more than 120/80 mm Hg to consider alternative approaches like transcendental medication as adjunct method to lower blood pressure.

Blood pressure (BP), even in healthy normotensive individuals, is dynamic, varies with a circadian periodicity, and is influenced by physiological and environmental factors. Abnormal 24-h BP patterns have been observed in many patients with hypertension (HTN), which may be overlooked if evaluations are based only on office BP measurements. Out of office BP measurements, such as Ambulatory Blood Pressure Monitoring and Home Blood Pressure Monitoring (ABPM and HBPM) is important for optimal BP management and are better predictors of adverse outcomes. However, HTN diagnosis and management are often based on relatively few clinic BP measurements, and there are no recommendations to guide clinicians managing patients with abnormal 24-h BP patterns in India. Thus, the present consensus statement aims to provide uniform evidence-based recommendations for the diagnosis and management of abnormal 24-h BP patterns. Strategies for screening for HTN based on the current prevalence trends in India have been suggested. Further, recommendations on the appropriate use of ABPM and HBPM in diagnosis and management of HTN are provided.

We are describing a case of repeated interventions performed during long-term follow-up. To the best of our knowledge, this is the only case report of 1 closed mitral valvotomy followed by 3 time balloon mitral valvotomy culminating ultimately to mitral valve replacement in 41 year follow-up.

Several studies including a small case-control (hypertriglyceridemic/normotriglyceridemic individuals) study by us revealed close association between rare S2 allele ofAPOC3 Sstl polymorphism and hypertriglyceridemia. With the understanding that Asian Indians are highly vulnerable to the adverse effects of hypertriglyceridemia, we extended the investigation and studied the frequency distribution of this polymorphism in 216 healthy volunteers from Northern plains of India. We found that more than 50% of the study population had one or two S2 allele. This may suggest that a larger fraction of this population is genetically predisposed to hypertriglyceridemia.

Lipoprotein Lp(a) excess has been identified as a powerful predictor of premature atherosclerotic vascular diseases. To evaluate this in a North-Indian population, 130 CAD patients and 130 controls were analyzed. The size of the apo(a) phenotypic isoforms was inversely proportional to Lp(a) concentrations. The mean concentration of Lp(a) in the CAD patients was 42±34 mg/dl whereas in the normal subjects it was much lower, 27±27 mg/dl. 157 subjects out of the total 260 subjects showed plasma levels of >20mg/dl. The frequency of high Lp(a) levels was much higher in patients(73%) than controls (43%). These data suggest (1) that there is heterogeneity of the Lp(a) polymorphism, (2) Higher Lp(a) levels were found in patients than in the controls, (3) Patients showed 1.5 fold increase in Lp(a) levels as compared to the controls. We conclude that low molecular weight apo(a) isoforms are significantly associated with increased risk of CAD in the North-Indian population.

An elevated level of plasma homocysteine, sulfur containing amino acid generated through demethylation of methionine has been widely accepted as a risk factor for cardiovascular disease (CVD). The increase can result from genetic and/or nutrient related disturbances in the remethylation or transsulfuration pathways for homocysteine metabolism. A common mutation (C677T) in the gene encoding for the enzyme 5, 10-methylenetetrahydrofolate reductase (MTHFR) or deficiency of the B vitamins namely folic acid, B(12), B(6) can lead to hyperhomocysteinemia.In the present study, we have investigated the incidence of the (C677T) MTHFR polymorphism in the North Indian males. 141 angiographically proven coronary artery disease (CAD) patients and 55 age and sex matched healthy volunteers were examined for the association between MTHFR gene polymorphism and CAD. The MTHFR genotyping was performed using polymerase chain reaction (PCR) followed by restriction-isotyping with Hinf 1 endonuclease. A trend for higher 'T' allele frequency (0.19) was observed in patients than in controls (0.16). However no significant association was found between C677T mutation and CAD severity. The lack of statistical significance could be due to the small sample size studied. Hence a larger study including various ethnic groups is warranted.

In practice, chronic heart failure is often not treated with angiotensin-converting enzyme inhibitors. One reason is the fear of first-dose hypotension. In the majority of patients, this condition is asymptomatic and the consequences are unexpected. Presently, little is known of its epidemiology.This was a prospective, 48-hour observational study of 160 patients with chronic heart failure due to systolic dysfunction, previously untreated with angiotensin-converting enzyme inhibitors, randomly drawn from the clinical practice of selected cardiologists across India. The primary outcome was a change in the mean arterial pressure during the first 24-hours after the first dose of an angiotensin-converting enzyme inhibitor. In 131/160 patients (81.9%) with no hypotensive symptoms, the incidence of first-dose hypotension (maximum 24-hour fall in mean arterial pressure greater than 10% from baseline) was 56/131 (42.7%). Pre-treatment diastolic pressure had a negative, independent association with 24-hour change in mean arterial pressure, accounting for 29% (R2=0.29, p0.01) of its variability, and its predictive value was greater with pro-drug angiotensin-converting enzyme inhibitors. The incidence of first-dose hypotension increased from 1 patient (4.8%) at a pre-treatment diastolic pressure of 50-70 mmHg to 35 patients (42.7%) at 71-90 mmHg, p0.01.The incidence of first-dose hypotension with angiotensin-converting enzyme inhibitors in outpatients with chronic heart failure due to systolic dysfunction is high. Pre-treatment diastolic pressure is an independent risk factor, and its predictive value increases with pro-drug angiotensin-converting enzyme inhibitors. This could help physicians to anticipate asymptomatic first-dose hypotension and increase the utilization of these agents in heart failure.

The association between Chlamydia pneumoniae infection and atherosclerosis has gained recognition. However, the nature of this association is controversial. The infective link may not be specific for atherosclerosis and may also exist in other nonatherosclerotic arterial diseases. We investigated patients with nonspecific aortoarteritis for serological evidence of prior Chlamydia pneumoniae infection.Fifty patients each of nonspecific aortoarteritis and coronary artery disease with angiographic evidence of significant (70%) coronary artery lesions were tested for the presence of IgG antibodies against Chlamydia pneumoniae by micro-immunofluorescence assay and compared with 50 age- and sex-matched normal healthy controls. The number of patients with nonspecific aortoarteritis who tested positive for Chlamydia pneumoniae antibodies (IgG) was not significantly different from controls (8 v. 7, p=ns). The mean titer amongst positive subjects in the two groups was also similar (1:40+/-40 v. 1:50+/-25; p=ns). Patients with coronary artery disease were significantly older than patients with nonspecific aortoarteritis and controls (53.2+/-5.8 v. 21.2+/-9.9 years and 24.5+/-5.2 years, p0.01 for both) and showed a higher seroprevalence of prior Chlamydia pneumoniae infection (18 v. 8 and 7, p0.05 for both). The mean IgG titers of patients with coronary artery disease who tested positive were also significantly higher than the other two groups (1:98+/-34 v. 1:40+/-40, p0.001 and 1:98+/-34 v. 1:50+/-25, p0.01, respectively).In patients with nonspecific aortoarteritis, the seroprevalence of prior Chlamydia pneumnoniae infection is not more than that in healthy individuals of the same age group, but is significantly lesser than that in patients with coronary artery disease. Thus Chlamydia pneumoniae infection may not be associated with all forms of chronic inflammatory arterial lesions.

The effects of chronic garlic intake on various endogenous antioxidant enzymes and lipid peroxidation on two major organs, the liver (L) and kidneys (K), were investigated. Wistar albino rats were fed with fresh garlic homogenate daily by gavage in three different doses (250, 500 and 1000 mg/kg/day) for 30 days. After this period, rats were sacrificed and liver and kidneys were harvested for biochemical estimation. In comparison to saline-treated rats, the 250 mg/kg/day dose significantly (P0.02) reduced thiobarbituric acid reactive substances (TBARS) (L: 187.48+/-9.23 vs 150.66+/-11.45; K: 177.38 15.88 vs 120.66+/-9.39 nmol/g wet. weight) and glutathione peroxidase (GPx) (L: 0.2438+/-0.05 vs 0.0046+/-0.0005; K: 0.1459+/-0.034 vs 0.0055+/-0.0003 U/mg protein). There was no change in catalase and reduced glutathione (GSH) but superoxide dismutase (SOD) increased significantly (P0.01) (L: 5.49+/-0.76 vs 18.38+/-2.26; K: 11.47+/-1.48 vs 21.22+/-3.19 U/mg protein). Both 500 and 1000 mg/kg/day doses significantly (P0.05) reduced endogenous antioxidants (catalase and SOD) without altering TBARS. A 1000 mg/kg/day dose of garlic caused marked histopathological and ultrastructural changes in both liver and kidneys. The results suggest that garlic in low doses has the potential to enhance the endogenous antioxidant status, although at higher doses a reversal of these effects is observed. The present study also highlights the potential ability of a high dose of garlic to induce morphological changes in the liver and kidneys, indicating the need to identify a safe dose range for garlic.

To the Editor: We have read with interest the article by Knight et al1 on the new technique of nonsurgical reduction as a therapeutic strategy in patients with hypertrophic obstructive cardiomyopathy (HOCM). We congratulate the authors for obtaining excellent results in their series of 18 patients. We have used the same technique at our center since early last year in a limited number of patients with excellent immediate reductions in left ventricular outflow tract (LVOT) gradients.2 3 However, we briefly discuss the course of our patients, highlighting the complications …

A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3 ) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India. DNA samples were analyzed by polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products were run on 3% agarose gel and visualized by ethidium bromide staining. Rare S2 allele was highly prevalent in our study population (0.313) as compared to the Caucasians (0.00–0.11). The genotypic distribution was in agreement with Hardy-Weinberg equilibrium . S2 allele was almost two times more prevalent in the HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43 (95%CI = 0.99–6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66–37.29, p = 0.0006) for developing HTG in comparison to S1S1 genotype. Our study shows a significant association between rare S2 allele and HTG in Asian Indians.

Oxidative stress plays a major role in the biochemical and pathological changes associated with myocardial ischemic-reperfusion injury (IRI). The need to identify agents with a potential for preventing such damage has assumed great importance. Chronic oral administration of raw garlic has been previously reported to augment myocardial endogenous antioxidants. In the present study, the effect of chronic oral administration of raw garlic homogenate on oxidative stress induced by ischemic-reperfusion injury in isolated rat heart was investigated. Raw garlic homogenate (125, 250 and 500 mg/kg once daily for 30 days) was administered orally in Wistar albino rats. Thereafter, hearts were isolated and subjected to IRI (9 min. of global ischemia, followed by 12 min of reperfusion; perfusion with K-H buffer solution; 37°C, 60 mm Hg.). Significant myocyte injury and rise in myocardial TBARS along with reduction in myocardial SOD, catalase, GSH and GPx were observed following IRI. Depletion of myocardial endogenous antioxidants and rise in TBARS were significantly less in the garlic-treated rat hearts. Oxidative stress induced cellular damage as indicated by ultrastructural changes, like disruption of myofilament, Z-band architecture along with mitochondrial changes were significantly less. The study strongly suggests that chronic garlic administration prevents oxidative stress and associated ultrastructural changes, induced by myocardial ischemic-reperfusion injury.

Effects of high altitude hypoxia on systolic time intervals were examined in 34 healthy men: 20 sea level residents studied at rest and at the end of 3 minutes steady isometric (handgrip) exercise at sea level and then serially for the first 5 days and on the tenth day, at an altitude of 3658 m, and I4 permanent residents at high altitude studied at high altitude. In the sea level residents there was a significant increase in the pre-ejection period (PEP), abbreviation of the left ventricular ejection time (LVET), both corrected for heart rate, and prolongation of the PEP/LVET ratio at high altitude. The maximum changes were seen on days 2 and 3; these parameters tended to approach sea level control values by the tenth day. The systolic time interval values of high altitude residents were similar to the control values of the sea level residents obtained at sea level but significantly different from the changes in the sea level values seen in the first 4 days at high altitude. It thus appears that while the high altitude residents do not show any left ventricular dysfunction as determined by systolic time intervals, healthy sea level residents when exposed to high altitude hypoxia show a significant depression of the left ventricular function for at least the first 4 days. This might be a contributing factor in the genesis of high altitude pulmonary oedema.

Changes in transthoracic electrical impedance (T.E.I.) due to high-altitude hypoxia (3,658 m) have been measured in 20 young, healthy Indian soldiers. They were first studied at sea level (198 m) and then rapidly transported by air to 3,658 m, where they were studied daily from day 1 to day 5 and then on days 8 and 10. The mean (+/-S.D.) T.E.I. at sea level (34.6+/-0.6Omega) fell sharply to 29.6+/-0.8Omega, 30.3+/-0.9Omega, and 30.5+/-1.1Omega on days 1, 2, and 3 (P0.001) and levelled off at 31.5+/-0.7Omega on day 10, which was comparable to the mean value obtained in 13 persons permanently resident at high altitude (32.2+/-0.7Omega). Five sea-level residents who had acute mountain sickness (A.M.S.) or high-altitude pulmonary oedema (H.A.P.O.) had a still lower mean value (22.5+/-1.1Omega). One normal healthy subject who at sea level had a T.E.I. of 34.7Omega developed H.A.P.O. when the T.E.I. fell to 21.1Omega. Ninety minutes after the administration of 80 mg of intravenous frusemide the value increased to 35.5Omega. In another subject with A.M.S. who received 40 mg of frusemide intravenously the T.E.I. rose from 21.9 to 33.2Omega.Since the study was non-invasive the changes in impedance could not be correlated objectively with alterations in either pulmonary blood volume or pulmonary extravascular water space. In the subject, however, with x-ray evidence of H.A.P.O. and a low T.E.I. intravenous frusemide produced a marked rise in T.E.I. together with clearing of the chest x-ray picture within 24 hours, indicating an inverse relationship between impedance and thoracic fluid volume. It is suggested that with further objective verification in man the measurement of T.E.I. may be a potentially promising technique for the early detection of increased pulmonary fluid volume.

Haemodynamic studies in 8 tribal patients from central India with veno-occlusive disease of the liver are reported. The disease was caused by eating cereals contaminated with seeds of a crotalaria species rich in toxic pyrrolizidine alkaloids similar to monocrotaline and fulvine. All patients showed raised hepatic venous wedge pressures and pressure gradients between hepatic venous wedge and free hepatic vein. Significant pressure gradients were also observed in the inferior vena cava. Right and left heart pressures were normal. Cardiac and stroke indices and ventricular work were significantly increased while systemic and pulmonary resistances were reduced. Hepatic blood flow was also reduced. Hepatic venograms were abnormal and the changes correlated well with the pressure gradients between hepatic venous wedge and free hepatic vein and with the histological changes in the liver.

Intracardiac frusemide given to seven patients recovering from high-altitude pulmonary oedema caused a significant reduction in the pulmonary blood volume before the onset of diuresis. This supports the suggestion that the mobilization of fluid from the pulmonary circuit is responsible for the relief of symptoms in some patients with pulmonary oedema even when a diuresis does not occur.

ACUTE mountain sickness and high altitude pulmonary oedema are two acute medical problems for troops in the Himalayan terrain who frequently shuttle between sea level and high altitudes (10,000–16,000 ft.). These two acute illnesses have some features in common: time lag (they rarely occur within 12 h of arrival at the altitude or 96 h after arrival), throbbing headache, muscular cramps and pulmonary congestion. We have studied the acute circulatory response to high altitude hypoxia and investigated the extent to which shifts in the circulating blood volumes, if any, could be related to the time lag and clinical features of these acute illnesses.

The immediate haemodynamic effects of peruvoside, a cardiac glycoside obtained from the Indian plant Thevetia neriifolia Juss, were studied in six patients with congestive heart failure. The drug was found to have an immediate and powerful positive inotropic and negative chronotropic effect, like ouabain, on the failing human heart. Oral peruvoside was also effective in the treatment of congestive heart failure when used on a short-term as well as a long-term basis. It therefore seems that peruvoside is a useful cardiac glycoside in the management of congestive heart failure in man as a quick-acting intravenous preparation. It is equally effective when used orally.