The influence of left ventricular filling pressure on atrial contribution to cardiac output.

The influence of left ventricular filling pressure on the atrial contribution filling pressure and atrial contribution was seen in studies done at baseline (PCW (r=-.53, p less than .025), as well as in studies done after PCW was modified by volume expansion and/or nitrates (r=-.53, p less than .005). At baseline, atrial contribution averaged 9.3 +/- 1.3 c.c./M.2 in patients with PCW less than 20 mm. Hg, while it was only 2.4 +/- 1.2 c.c./M.2 in patients with PCW greater than or equal to 20 mm. Hg (p less than .005). Atrial contribution was significantly greater in patients who had no history of heart failure when they were volume loaded to a PCW above 20 mm. Hg than in patients with impaired ventricular function whose baseline PCW was above 20 mm. Hg. Thus, atrial contribution tends to be less effective in augmenting cardiac output when filling pressure is already elevated, particularly in patients with impaired left ventricular function.     

The noninvasive diagnosis of right ventricular infarction

We evaluated scintigraphy and echocardiography for the diagnosis of right ventricular (RV) infarction. Of 26 patients with acute transmural myocardial infarction (MI), six with inferior MI had abnormal radionuclide uptake localized to the RV free wall on infarct scintigraphy or segmental akinesis of the RV free wall on gated radioangiography or both. These six patients with RV involvement (group I) were compared with the remaining nine with inferior MI (group II) and 11 with anterior MI (group III). RV/LV area ratios determined radioangiographically were significantly greater in group I than group II in diastole and systole. Echocardiographic RV enddiastolic dimension and RV/LV end-diastolic dimension ratio were significantly greater and RV stroke work index was significantly lower in group I than in group II. Predominant RV involvement in inferior MI may occur commonly. Anatomic and functional evidence of this diagnosis can be obtained noninvasively.     

Vasodilator therapy

As detailed in this review, it is apparent that vasodilator therapy is an important new medical treatment for both acute and chronic heart failure. The specific hemodynamic effect of each vasodilator is related to its relative dilating effect on arterioles and systemic veins. The vasodilators that predominantly dilate arterioles (e.g., hydralazine) generally produce an increase in cardiac output with little effect on an elevated pulmonary capillary wedge pressure. The vasodilators that predominantly dilate systemic veins (e.g., nitroglycerin) will reduce pulmonary capillary wedge pressure with little effect on forward cardiac output. Some vasodilators like nitroprusside have balanced effects on arterioles and veins, and produce both these beneficial hemodynamic effects.

As long as the blood pressure is within reasonable limits, vasodilators are extremely effective in patients with acute heart failure, including those with acute pulmonary edema. When vasodilators are administered to patients with an elevated left ventricular filling pressure, there is generally no accompanying tachycardia, because the patients are on the plateau region of their ventricular function curve. When administered to patients with a left ventricular filling pressure less than 15 mm Hg, however, a reduction in filling pressure down the ascending limb of the ventricular function curve may result in a reduction in stroke volume, which may be accompanied by a compensatory tachycardia. This rationale illustrates the importance of administering vasodilators to patients with an elevated left ventricular filling pressure.

More recently, vasodilators have found a role in the therapy of patients with chronic congestive heart failure. Their efficacy suggests the presence of an excessive systemic vascular resistance in these patients that may not be in the best interests of the overall function of the cardiovascular system. Reduction of systemic vascular resistance with a vasodilator such as hydralazine is often effective in markedly increasing forward cardiac output.

Vasodilators may also be helpful in mechanical defects such as mitral regurgitation, ventricular septal defect and aortic regurgitation. Since vasodilators and inotropic agents work by different mechanisms, their effects can be beneficially additive in the patient with acute or chronic heart failure. The most serious complication of vasodilator therapy is hypotension. Other side effects are specific to the individual vasodilator being used.

In conclusion, the vasodilator drugs form an important new class of agents that can be beneficial to patients with acute or chronic heart failure. It is probable in the future that newer agents will become available and will be used as frequently as digitalis in the treatment of such patients.     

A Novel Role of SLC26A3 in the Maintenance of Intestinal Epithelial Barrier Integrity

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Termites as Structural Pest: Status in Indian Scenario

In this status paper, impact of termites as serious structural insect-pests is highlighted with relevant information in Indian context. Worldwide, more than $40 billion was estimated towards the termite damage. Study revealed at least thirteen species of termites belonging to three families are closely associated with structural damage in India. Heterotermes indicola (Rhinotermitidae: Isoptera) was discussed as the key termite species causing structural damage with substantial impact (even with astounding cases of abandoning houses by victimized villagers). Swarming, the most important sign of termite infestation in and around buildings/structures is discussed. A nation-wide scenario of termite damage in various buildings, public places, dams and dykes, agri-horticultural constructions and timber-in-service are presented. Sustainable termite control in the light of present and upcoming eco-technologies is identified as the major focal point. Use of termiticides as recognized and recommended by Indian Standards, Insecticide Act (1968) and United Nation Environment Program for management of termites in pre- and post-construction stages of various buildings and other structures are recorded with relevance of application and dose. Termite management technologies like use of borate, bait and barrier (3B) are briefed; with pest-control industry-invented devices such as termatrac are brought into focus along with indigenous traditional knowledge of termite control. Status of termite R&D in India is discussed in various institutional and web-based levels along with recognizing research gaps. The present study is a pioneer approach in its kind which can be a platform to formulate compact eco-friendly, environmentally sustainable and economic module of termite control interventions indoor.     

Preparation of macroporous scaffolds with holes in pore walls and pressure driven flows through them

Controlling the pore architecture in macroporous scaffolds has important implications for their use as reactor packings and as catalyst supports. We report the preparation of a macroporous structure, where the pore walls are perforated by holes. These materials are prepared by modification of the ice-templating protocol developed in our group. We freeze a dispersion of colloidal silica, polymer and cross-linker in a water/acetonitrile medium and allow crosslinking to proceed in the frozen state. The presence of a small fraction of acetonitrile (varying between 1.6% to 6.4%) results in the formation of holes in the pore walls. Increasing the acetonitrile concentration changes the pore size distribution, and produces smaller pores on average. This also results in an increasing fraction of the wall area being covered by small pores, of the order of a few microns in size. Perforation of the walls by pores does not change the overall porosity or modulus of the scaffolds. However, the introduction of pores leads to a drastic reduction in the pressure drop required to pump liquid through the scaffolds. The observed residence time distribution (RTD) in the scaffolds is represented by two plug flow reactors (PFRs) in parallel. The RTD results indicate that increasing the hole fraction in the pore walls results in increased channelling which explains the aforementioned decreased pressure drop during pressure driven flow.

Controlling the pore architecture in macroporous scaffolds has important implications for their use as reactor packings and as catalyst supports.     

Non‐alcoholic steatohepatitis induces non‐fibrosis‐related portal hypertension associated with splanchnic vasodilation and signs of a hyperdynamic circulation in vitro and in vivo in a rat model

Introduction: Steatosis, without fibrosis, may lead to changes in liver blood flow, which are poorly understood, and to date have not been correlated to portal pressure and related haemodynamics. Aims: To study the temporal relation between progressive steatosis, portal pressure, systemic haemodynamics, vascular responsiveness, mesenteric and portal blood flow in methionine–choline‐deficient diet (MCDD)‐fed rats. Methods: Male Wistar rats fed the MCDD were examined at week (w) 0‐1‐2‐3‐4‐5‐6‐7‐8, respectively, including systemic haemodynamics and portal pressure. At w0‐4‐8, in vivo blood flow was measured in the portal vein and the superior mesenteric artery. Dose–response curves to phenylephrine (PE) were established in abdominal aortic rings. Results: Histology showed 100% steatosis from w3 on. Fibrosis was absent. Significant inflammation was nearly absent upon w4. Portal pressure slightly increased at w2, reached a maximum at w4 [9.4 ± 0.3 vs 2.9 ± 0.6 mmHg at w0 (P=0.003)] and remained stable upon w8. Mean arterial blood pressure (MABP) decreased from w2 on [98.7 ± 5.7 mmHg on w4 compared with 123.8 ± 1.8 on w0 (P=0.002)]. Portal flow increased from 1.85 ± 0.11 to 3.07 ± 0.44 ml/min/100 g on w0 and w8 respectively (P=0.039). Mesenteric artery flow increased from 3.40 ± 0.26 to 4.56 ± 0.30 ml/min/100 g on w0 and w8 respectively (P=0.043). Vascular responsiveness to PE gradually decreased from 138 ± 3% on w0 to 110 ± 5% on w4 (P=0.013). Conclusion: Steatohepatitis induces significant portal hypertension (PHT) in the absence of fibrosis, associated with an increase in mesenteric arterial and portal venous flow, arterial hyporesponsiveness to vasoconstrictors and a decrease in MABP, indicating the presence of splanchnic vasodilation and hyperdynamic circulation. These alterations resemble those seen in cirrhotic PHT.     

Bayesian estimates of the prevalence of β-thalassemia trait in voluntary blood donors of central India: a survey

Early detection of β-thalassemia (β-thal) trait is important. Voluntary blood donors represent an important group who are accessible and cooperative for this purpose. However, the usefulness of this population in β-thal trait detection programs has not been studied in India. We conducted a hematological survey of 5,045 blood donors who visited the Bhopal Memorial Hospital & Research Centre, Bhopal in central India. Using robust Bayesian methods, we estimated the prevalence of β-thal trait. The overall prevalence of β-thal trait in the study population was 9.59% [95% confidence interval (95% CI) 8.78-10.4%]. The prevalence of β-thal trait varied across the states of origin and within the state of Madhya Pradesh. We observed a cline effect for β-thal trait prevalence in relation to the latitude (p = 0.024). We conclude that blood donors offer an attractive adjunct to β-thal trait detection in national programs. Our study also offers insights into the β-thal trait gene flow and migration in India.     

The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism

Cancer cells preferentially metabolize glucose by aerobic glycolysis, characterized by increased lactate production. This distinctive metabolism involves expression of the embryonic M2 isozyme of pyruvate kinase, in contrast to the M1 isozyme normally expressed in differentiated cells, and it confers a proliferative advantage to tumor cells. The M1 and M2 pyruvate-kinase isozymes are expressed from a single gene through alternative splicing of a pair of mutually exclusive exons. We measured the expression of M1 and M2 mRNA and protein isoforms in mouse tissues, tumor cell lines, and during terminal differentiation of muscle cells, and show that alternative splicing regulation is sufficient to account for the levels of expressed protein isoforms. We further show that the M1-specific exon is actively repressed in cancer-cell lines—although some M1 mRNA is expressed in cell lines derived from brain tumors—and demonstrate that the related splicing repressors hnRNP A1 and A2, as well as the polypyrimidine-tract-binding protein PTB, contribute to this control. Downregulation of these splicing repressors in cancer-cell lines using shRNAs rescues M1 isoform expression and decreases the extent of lactate production. These findings extend the links between alternative splicing and cancer, and begin to define some of the factors responsible for the switch to aerobic glycolysis.