Indoor air quality and its relationship with cluster type in urban Pakistani households.

OBJECTIVE: To assess the levels and predictors of formaldehyde, nitrogen dioxide (NO2), carbon monoxide (CO) and fine particulate matter with diameter less than 2.5 µm (PM2.5) in Karachi, Pakistan.METHODS: A total of 1629 households were selected through multistage cluster sampling in a community-based cross-sectional survey. Formaldehyde, NO2 and CO levels were measured using YesAir Indoor air monitor and for PM2.5, UCB-PATS (University of California Berkeley Particle and Temperature Sensor) was used. Clusters were classified either as planned (areas of planned housing) or unplanned (informal settlements).RESULTS: We found the median concentrations to be as follows: formaldehyde, 0.03 ppm (IQR 0.00-0.090); CO, 0.00 ppm (IQR 0.00-1.00); NO2, 0 ppm (IQR 0.00-0.00) and PM2.5, 0.278 mg/m³ (IQR 0.162-0.526). We found a significant association of the upper quartiles of formaldehyde and PM2.5 levels with type of cluster. The risk of obtaining formaldehyde and PM2.5 levels in the upper quartile was higher in unplanned clusters than in planned clusters (adjusted odds ratio [aOR] 33.0, 95% CI 4.02-271.5 and aOR 0.10, 95% CI 0.001-0.16, respectively). No significant association was observed between levels of CO and cluster type (aOR 0.84, 95%CI 0.62-1.14).CONCLUSION: This study reports high levels of indoor air pollutants in Karachi, with considerable variation across planned vs. unplanned clusters.

Biphasic action of aldosterone on Akt signaling in cardiomyocytes.

Both aldosterone and Akt signaling play pivotal roles in the pathogenesis of heart failure. However, little is known about the correlation between them. We herein investigated whether aldosterone interacts with Akt signaling in a coordinated manner in cardiomyocytes. Neonatal rat cardiomyocytes were stimulated with aldosterone for either a short (10-min) or long (24-h) time. The phosphorylation of Akt and its downstream effector, GSK3ß, were transiently increased after short-term stimulation, which was blocked by either PI3K or Na(+)/H(+) exchanger inhibitors, but not by the mineralocorticoid receptor antagonist, eplerenone. Long-term stimulation also significantly increased Akt-GSK3ß phosphorylation and this effect was reduced by eplerenone. Thus, these results suggest that aldosterone activates Akt signaling via a biphasic reaction that occurs through different cascades. To understand the significance of the rapid action of aldosterone, cardiomyocytes were exposed to hydrogen peroxide for from 10 to 60 min. A short-term aldosterone stimulation (for up to 30 min) significantly protected cardiomyocytes from oxidative stress-induced cellular damage. Eplerenone did not abrogate this beneficial effect, while a PI3K inhibitor did. Therefore, during the early phase, aldosterone has favorable effects on cardiomyocytes, partly by acute activation of a mineralocorticoid receptor-independent cascade through the Na(+)/H(+) exchanger, PI3K, and Akt. In contrast, its persistent activity produces pathological effects partly by chronic Akt activation in a mineralocorticoid receptor-dependent manner.

Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors.

OBJECTIVES: The goal of this study was to determine: 1) whether bradykinin (BK) directly stimulates tissue plasminogen activator (tPA) secretion in human coronary circulation, and 2) whether angiotensin-converting enzyme (ACE) inhibition favorably alters the fibrinolytic balance regulated by BK. BACKGROUND: Bradykinin is a potent stimulator of tPA secretion in endothelial cells; however, the effect of BK on tPA release in the human coronary circulation has not been studied. METHODS: Fifty-six patients with atypical chest pain were randomly assigned to two groups: 25 patients were treated with the ACE inhibitor enalapril (ACE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE inhibitor group). Graded doses of BK (0.2, 0.6, 2.0 microg/min), acetylcholine (ACh) (30 microg/min) and papaverine (PA) (12 mg) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS). RESULTS: Bradykinin induced similar increases in CBF in both groups. The net tPA release induced by BK was dose-dependently increased in both groups, and the extent of that increase in the ACE inhibitor group was greater than that in the non-ACE inhibitor group. Bradykinin did not alter plasminogen activator inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neither ACh nor PA altered tPA levels or PAI-1 levels in either group. CONCLUSIONS: Intracoronary infusion of BK stimulates tPA release without causing any change in PAI-1 levels in the human coronary circulation. In addition, this effect of BK is augmented by an ACE inhibitor.

Angiographically documented coronary steal phenomenon evoked by the intracoronary infusion of bradykinin.

While studying flow-dependent coronary dilation using a Doppler flow velocity guidewire, total occlusion of a stenosed segment of the left circumflex artery during the intracoronary infusion of bradykinin was angiographically documented. Total occlusion was not demonstrated during intracoronary infusion of bradykinin after angioplasty. This is angiographic confirmation of the coronary steal phenomenon that has been previously described in the field of stress scintigraphy.

Coronary vasomotor responses to bradykinin and acetylcholine in patients with coronary spastic angina.

It is unclear whether coronary endothelial function is linked to the pathogenesis of coronary spastic angina (CSA), so the present study examined the coronary vasomotor responses to acetylcholine (ACh) and bradykinin (BK) in 23 patients with CSA, 26 patients with CSA+coronary artery disease (CAD), and 21 control patients. Acetylcholine induced vasospasm of the left coronary artery in all of the patients with CSA, but not in any of the control patients. The changes in dilatation of the left coronary artery in response to bradykinin at doses of 0.2, 0.6 and 2.0 microg/min in the CSA group were significantly greater than those in the other 2 groups. The ratio of epicardial coronary vasodilations induced by BK to those induced by nitroglycerin did not differ among any of the groups. Bradykinin caused a similar increase in coronary blood flow in the control group and CSA group, but had less of an effect in the CSA+CAD group. In conclusion, the vasorelaxing effect of BK was preserved not only in epicardial spasm coronary arteries induced by ACh, but also in resistance coronary arteries distal to the spasm arteries in patients with CSA. The coronary vasodilation response induced by BK may not deteriorate until coronary atherosclerosis advances in patients with CSA.

Effects of intravenous nicorandil on coronary circulation in humans: plasma concentration and action mechanism.

We investigated the cardiovascular profile of nicorandil, an antianginal agent, in humans. Pharmacologically, nicorandil acts as both an adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channel opener and a nitrate. We examined which of these mechanistic components has a predominant vasodilatory effect at clinical doses. Fourteen patients underwent cardiac catheterization. The effects of the continuous intravenous infusion of nicorandil (12 mg/45 min) were examined in angiographically normal coronary arteries. Coronary vascular resistance was calculated from coronary artery diameter and coronary blood flow velocity measured using an intravascular Doppler catheter. We compared the hemodynamic responses to nicorandil with those to the intracoronary injection of nitroglycerin (250 microg) and papaverine (12 mg). The epicardial coronary arteries responded to nicorandil at the lowest plasma concentration examined (dilation of +14.0 +/- 3.3% at approximately 170 ng/ml), whereas dilation of the coronary resistance arteries (i.e., a decrease in coronary vascular resistance) took place only at higher concentrations (>200 ng/ml). Nitroglycerin caused no further changes in coronary artery diameter or coronary vascular resistance. Papaverine caused no further increase in coronary artery diameter, but markedly decreased coronary vascular resistance (1.6 +/- 0.3 to 0.4 +/- 0.1 mm Hg/ml/min; p < 0.05). Nicorandil significantly decreased pulmonary capillary wedge pressure (i.e., reduced cardiac preload) at a plasma level of >200 ng/ml, but did not change either systemic or pulmonary vascular resistance. Thus nicorandil preferentially dilated epicardial coronary arteries rather than coronary resistance arteries, and had a stronger effect on preload than on afterload. These changes in human coronary hemodynamics suggest that the nitrate actions of nicorandil as a coronary vasodilator predominate over those as a K(ATP) opener.

Brain natriuretic peptide predicts chronic atrial fibrillation after ventricular pacing in patients with sick sinus syndrome.

Chronic atrial fibrillation (AF) is one of the main complications of sick sinus syndrome (SSS). As previously reported, plasma brain natriuretic peptide (BNP), reflects hemodynamic changes in different pacing modes, as does plasma atrial natriuretic peptide (ANP), so the present study investigated whether plasma BNP or ANP can predict chronic AF after single-chamber ventricular (VVI) pacemaker implantation in patients with SSS. Plasma ANP and BNP levels were measured before and 1-3 months after implantation in 99 SSS patients. Long-term follow-up was conducted with chronic AF as an endpoint. Chronic AF occurred in 19 patients during a mean follow-up of 5.1 years. Plasma ANP and BNP were significantly higher in the patients who developed chronic AF after implantation than in those who did not, despite similar ANP and BNP levels between the 2 groups before implantation. Post-implant high BNP and a history of paroxysmal AF were independent predictors of chronic AF by a multivariate Cox proportional hazards analysis. Plasma BNP can predict the development of chronic AF after VVI pacemaker implantation in patients with SSS because increased levels may reflect latent hemodynamic abnormalities, which may contribute to the development of AF after VVI pacemaker implantation.

Plasma brain natriuretic peptide as a biochemical marker for atrioventricular sequence in patients with pacemakers.

We hypothesized that plasma brain natriuretic peptide, like plasma atrial natriuretic peptide, may reflect hemodynamic changes elicited by different cardiac pacing modes. The aim of this study was to investigate whether plasma brain natriuretic peptide could be influenced by different pacing modes or electrical stimulation. The subjects consisted of 164 patients with permanent pacemakers (52 VVI, 30 AAI, 82 DDD pacemakers) and unimpaired heart function. Patients with atrial fibrillation or spontaneous beats were excluded. Plasma atrial natriuretic peptide and brain natriuretic peptide levels were measured at a rate of 70 beats/min after 45 minutes in the supine position. Under ECG monitoring, the pacing mode was switched from DDD to VVI in 12 patients and from DDD to AAI in 4 patients with a dual chamber pacemaker. Plasma atrial natriuretic peptide and brain natriuretic peptide levels were also measured 30 minutes, 60 minutes, and 1 week after mode switching. Plasma atrial natriuretic peptide and brain natriuretic peptide levels were significantly higher in the nonphysiological pacing group than in the physiological pacing group, whereas these values were similar in the DDD and AAI pacing groups. One week after switching from DDD to VVI, plasma atrial natriuretic peptide and brain natriuretic peptide levels were significantly increased, however no significant changes were observed after switching to AAI. Based on a multivariate regression analysis of noninvasive clinical parameters, only a low plasma brain natriuretic peptide was significantly correlated with physiological pacing. We conclude that: (1) plasma brain natriuretic peptide, like atrial natriuretic peptide, is influenced by the pacing mode, but is not influenced by electrical stimulation; and (2) low plasma brain natriuretic peptide is important in relation to physiological pacing.

Long-term beneficial effect of late reperfusion for acute anterior myocardial infarction with percutaneous transluminal coronary angioplasty.

BACKGROUND: Although the short-term and long-term beneficial effects of early coronary revascularization by primary PTCA or thrombolytic therapy have been established for acute myocardial infarction, thrombolytic therapy >24 hours after the onset of acute myocardial infarction has not been shown to improve clinical outcome. The purpose of this study was to assess the effect of late revascularization by primary PTCA over a 5-year period. METHODS AND RESULTS: Eighty-three patients with initial Q-wave anterior myocardial infarction >24 hours after onset were randomized into a PTCA group (n=44) and a no-PTCA group (n=39). Long-term follow-up was conducted with regard to end points, which included cardiac death, nonfatal recurrence of myocardial infarction, and development of congestive heart failure. Left ventricular ejection fraction and regional wall motion at 6 months after myocardial infarction were similar in the 2 groups. Left ventricular end-diastolic and end-systolic volume indexes were significantly smaller in the PTCA group than in the no-PTCA group (P<0.0001). With cardiac events as end points, a 5-year Kaplan-Meier event-free survival analysis revealed that the no-PTCA group had a worse prognosis than the PTCA group (P<0.0001). Patency of the infarct-related artery, left ventricular ejection fraction, end-diastolic volume index, and end-systolic volume index were significantly associated with cardiac events by a Cox proportional hazards analysis (hazard ratios 0.120, 0.845, 1.065, and 1.164, respectively). CONCLUSIONS: In initial Q-wave anterior myocardial infarction, we conclude that even with late reperfusion, PTCA had beneficial effects on cardiac events over the 5-year period after myocardial infarction, with the prevention of left ventricular dilation after myocardial infarction being a possible mechanism.

Plasma renin activity in acute renal failure induced by norepinephrine infusion in unilaterally nephrectomized dogs.

Plasma renin activity was determined by bioassay prior to, during and following a 2-hour infusion of norepinephrine into the renal artery in unilaterally nephrectomized dogs in order to examine the role of renin-angiotensin system in norepinephrine-induced ARF. ARF was induced in 5 of 8 dogs receiving 0.75 microgram/kg/min of norepinephrine, but not in the remaining 3 dogs and 2 dogs infused with 0.6 and 0.4 microgram/kg/min of norepinephrine. There proved no difference in plasma renin activity in renal venous blood between the dogs with and without ARF when followed up to 2 h after the discontinuation of the infusion. The same results were obtained when the plasma renin activity in the foreleg vein was followed at 24, 48 and 72 h after the infusion. The renin-angiotensin system does not seem to contribute to the reduction of renal function in norepinephrine-induced ARF in dogs.

Plasma catecholamine levels in the coronary sinus, aorta and femoral vein of subjects undergoing cardiac catheterization at rest and during exercise.

Plasma catecholamine (CA) levels in the coronary sinus (CS), aorta (Ao) and femoral vein (fv) were simultaneously measured in 22 patients with various heart diseases at rest and during handgrip exercise (IHG). The mean resting levels of plasma norepinephine (NE) in CS, Ao and FV were 359 +/- 49 (SEM) pg/ml, 290 +/- 27 and 234 +/- 24, respectively. The corresponding values of epinephrine (E) were 127 +/- 18 pg/ml, 186+/- 30 and 97 +/- 11, respectively. The E values in Ao were significantly greater than those in CS and in FV (p less than 0.05). IHG exercise induced an obvious elevation of plasma CA levels in every portion of the circulation studied. The mean increments of NE concentration were 81%, 54% and 67% of the resting levels at CS, Ao and FV, respectively, while IHG induced elevation of E were 70% of the resting values at each portion studied. Significant correlations were observed between individual CA concentrations in CS and in Ao, and also between those in Ao and in FV at rest. Under raised sympathoadrenal conditions, however, individual values of NE in CS failed to correlate signficantly to those in Ao and in FV, respectively. The NE output from CS was limited to only 3% and 5% of those in Ao at rest and during IHG, respectively. An actual mean increment of NE on its passing through the coronary circulation was only 2% or less of NE output in ao at both stages. It appears, thus, to be untenable that the cardiac tissue is one of the major source of circulating CA at physiological condition. From these reasons, the direct measurement of NE levels in CS may be mandatory, when plasma CA assay is designed for the purpose of studying the role of the sympathetic nerve activity in the regulation of cardiac function.

Effect of various states of hydration on plasma ADH and renin in man.

To investigate the interaction between antidiuretic hormone (ADH) and renin-angiotensin system, plasma ADH and plasma renin activity (PRA) were determined in normal subjects (n = 10) under various hydrated states. Four experimental conditions, i.e., water loading, infusion of hypertonic saline, acute dehydration induced by furosemide and postural changes, were chosen. 1. Upright posture decreased plasma volume by 9.5 +/- 0.9% without significant changes in plasma osmolality. PRA increased from 5.2 +/- 0.7 to 8.3 +/- 0.8 ng/ml. However, plasma ADH did not change significantly (1.9 +/- 0.3 to 1.8 +/- 0.2 muU/ml). 2. When furosemide was administered intravenously under this condition, both plasma ADH and PRA increased to 3.1 +/- 0.5 muU/ml and 15.5 +/- 1.6 ng/ml with 11.2 +/- 1.1% decrease in plasma volume. Plasma osmolality did not change significantly. 3.Water load resulted in a decrease in plasma osmolality from 282.6 +/- 0.9 to 278.6 +/- 1.2 mOsm/kg without significant change in plasma volume. Significant decrease in plasma ADH level from 2.6 "/- 0.4 to 0.6 "/- 0.1 muU/ml was found, but PRA (7.8 +/- 1.1 ng/ml) did not change (6.3 +/- 1.0 ng/ml). 4. Hypertonic saline infusion brought about an increase in plasma osmolality to 290.1 +/- 0.8 mOsm/kg with simultaneous increase in plasma volume by 6.7 +/- 1.3%. Plasma ADH level also increased to 2.4 +/- 0.3 muU/ml, while PRA decreased to 4.2 +/- 0.3 mg/nl. Accordingly, significant correlation between changes in PRA and plasma ADH level, was not observed. We suggest that plasma osmolality is the dominant variable in regulating plasma ADH level, but in the presence of a sufficient degree of hypovolemia, the osmotic domination was overcome. On the other hand, PRA was strongly influenced by changes in effective blood volume other than changes in plasma osmolality.