Rolipram reduces the inotropic tachyphylaxis of glucagon in rat ventricular myocardium

Glucagon increases cardiac contractility through G_s protein-coupled glucagon receptors, but the inotropic responses fade. The fade could be due to receptor desensitisation or to the action of phosphodiesterases (PDE), or to both mechanisms. We investigated the effects of the PDE4 inhibitor rolipram (1 M) on the inotropic and cAMP-responses to glucagon in paced right ventricular strips of the rat heart. Responses to the partial agonist dobutamine, mediated through ₁-adrenoceptors, were studied for comparison. Glucagon increased contractility (–logEC₅₀M=7.3 for maximum responses with E_max=32% of the response to 9 mM Ca²⁺), but the responses tended to fade (–logEC₅₀M=7.1 for faded responses with E_max=11.5%). Dobutamine (–logEC₅₀M=5.8, E_max=56%) produced positive inotropic effects that did not fade. Rolipram did not affect basal contractility and cAMP levels. Rolipram enhanced the contractile responses to glucagon and reduced fade (–logEC₅₀M=7.5 and 7.3 with E_max=74% and 45% for maximum and faded responses respectively). The response to glucagon (0.1 M) completely faded in the absence of rolipram, but only partially faded and then remained stable in the presence of rolipram (1 M). Rolipram enhanced contractile responses to dobutamine (–logEC₅₀M=6.0, E_max=75%). Dobutamine (3 M), but not glucagon (0.1 M), increased tissue levels of cAMP. Consistent with the inotropic data, rolipram caused glucagon to augment cAMP and enhanced the effects of dobutamine. Thus, PDE4 activity limits the responses mediated through both glucagon receptors and ₁-adrenoceptors. PDE4-catalysed hydrolysis of cAMP contributes to the inotropic tachyphylaxis of glucagon.     

Association of right ventricular dysfunction and Cheyne-Stokes respiration in patients with chronic heart failure

Cheyne-Stokes respiration (CSR) is present in up to 40% of patients with congestive heart failure (CHF) and is an independent risk factor for increased overall mortality. We examined whether CSR is associated with right ventricular (RV) dysfunction in CHF patients. Parameters of RV function were assessed by two-dimensional echocardiography and tissue velocity imaging in 42 patients (aged 23-75 years) with a left ventricular (LV) ejection fraction below 40%. Respiratory polygraphy revealed CSR with an central apnea-hypopnea index (CAHI) >10 h-1 in 13 of the 42 patients (31%). Demographic characteristics did not differ among the patient groups. The velocity of the tricuspid annular systolic motion (TASM), a parameter reflecting systolic RV function, was significantly reduced in CHF patients with CSR (10.5 +/- 2.3 cm s-1) compared with those without CSR (15.0 +/- 5.1 cm s-1, P = 0.004), and was inversely associated with the CAHI (y = 15.2-0.2x; r = 0.46, P = 0.003). The RV dimensions were significantly increased and the fractional RV area changes significantly reduced in CHF patients with CSR (33 +/- 17 versus 48 +/- 20%; P = 0.04). Doppler parameters of pulmonary artery flow indicate higher pulmonary artery pressures in CSR patients compared with patients without CSR, which is also reflected by an increased RV free-wall thickness in CSR patients (6.5 +/- 1.1 vs. 5.3 +/- 1.3 mm; P = 0.05). Parameters of systolic LV function, forced expiratory volume in 1 s (FEV1), and PaO2 and PaCO2 were not different among patients with or without CSR. In conclusion, CSR is associated with depressed systolic RV function and increased RV dimensions in CHF patients. Future studies will show whether optimized treatment of CSR will improve RV function.     

Shape of the left ventricle and its computer modelling

A simple computer program was made to draw different left ventricle shapes in order to support the theory of elongation and to get a visual presentation of the shape of the left ventricle. Experimental data, obtained from echocardiography and Simpson's rule, were used for this program. The results yielded different shapes under different physiological circumstances, indicating the sensitivity of the method. It was concluded that these figures (shapes) support the use of elongation as a shape index.     

Influence of Changes in Intrathoracic and Central Venous Pressure on Cardiac Filling Dynamics

Changes in the ratio between intrathoracic and central venous pressure were studied in narcotized cats under conditions of constant positive or negative pressure ventilation. Transformation of elastic characteristics in the respiratory system caused by changes in intrathoracic pressure led to inversion of the ratio between transpulmonary intrathoracic and central venous pressure determining right atrial filling pressure.     

Degenerative Changes and Cell Death in Long-Living Homo- and Heterotopic Transplants from Embryonic Germ Layers of Rat Neocortex

Morphological study of allotransplants of rat embryonic neocortex 14-18 months after transplantation into the neocortex, lateral cerebral ventricle, and sciatic nerve of adult animals revealed death of nerve and glial cells in the delayed postoperation period independently on the site of transplantation. After heterotopic transplantation the count of degenerated neurons was 2 times higher that after homotopic transplantation. In heterotopic transplants a considerable number of grafted neurons underwent reversible and irreversible degenerative changes accompanied by their premature aging. Neuronal death is probably determined by insufficiency of trophic influence from afferent structures and target tissues. We hypothesized that antiapoptotic preparations can be used for prevention of transplanted cell death. It was also found that degeneration of neurons was associated with impaired vascularization of transplants and pronounced immune reaction of the recipient in late posttransplantation period. Transplantation of embryonic brain structures can serve as a model system in studies concerning involutive and pathological processes in the central nervous system and in the search for factors improving survival of neurons.     

Arrhythmogenic right ventricular dysplasia in the elderly

Arrhythmogenic right ventricular dysplasia (ARVD) is a syndrome characterized by recurrent ventricular tachycardia. However, cases of ARVD have also presented as dilated cardiomyopathy later associated with ventricular arrhythmias. Histologically, this syndrome manifests as a fibrofatty replacement of the RV myocardium, predisposing the heart to ventricular arrhythmias. ARVD was once considered a disease of the young, but may be underrecognized in the older population. This report presents two cases of elderly men with newly symptomatic ARVD, believed to represent the oldest patients with ARVD described in the literature to date. The diagnosis of ARVD should be considered in individuals of all ages who present with a clinical syndrome consistent with ARVD and supportive evidence on ECG.     

Trisomy 21 with XYY

A case of double aneuploidy involving chromosome 21 and Y is reported in an eight-month-old infant with developmental delay and failure to thrive. Patient had all classical phenotypical features of trisomy 21 except, absence of epicanthal folds. The diagnosis was confirmed by cytogenetic study performed on peripheral blood leucocyte culture using G-banding. Literature review revealed only 17 cases of XYY and trisomy 21 reported so far. No such case is reported in Indian literature. Relevant literature is reviewed and possible effects of trisomy 21 on XYY and that of XYY on trisomy 21 has been discussed. A routine chromosomal study even in patient with classical features of Down syndrome has been advocated. Interestingly, our patient also had left to right shunts at atrial and ductal level and tricuspid regurgitation. Given the rarity of the disorder and scanty published data the incidence, phenotype and recurrence risk are difficult to establish.     

Medical care inconsistent with patients' treatment goals: association with 1-year Medicare resource use and survival

OBJECTIVES: To describe how frequently seriously ill persons perceive that the care they receive is inconsistent with treatment preferences and the effect on 1-year resource utilization. SETTING: Five U.S. teaching hospitals. DESIGN: Secondary analysis of interview data. PARTICIPANTS: Seriously ill Medicare beneficiaries. MEASUREMENTS: Interviews about patients' preferred approaches to care and whether they perceived care was consistent with these preferences. Part A and B costs for up to 1 year, adjusted for cost differences across hospitals and over time and for 1-year survival. RESULTS: Forty percent of the 1,185 study patients expressed a preference for treatment to focus on extending life, whereas 60% expressed a preference for comfort care. Eighty-six percent of the patients who wanted aggressive treatment reported that care was consistent with their preferences, but only 41% of those who preferred comfort care reported that care was consistent with their preferences. More than one-third of those with a preference for comfort care (35%) reported that the medical care that they received was inconsistent with their goals; 24% were unsure of treatment goals. Those who preferred comfort care but believed that their care was inconsistent with their wishes had higher estimated mean 1-year costs than those who believed that their care was consistent with their wishes (92,442 US dollars vs 52,098 US dollars, P < .001). Even after adjusting for differences in disease severity, age, gender, race, functional status, income, and years of education, adjusted costs were 1.4 times (95% confidence interval = 1.2-1.6) higher. However, 1-year survival was lower in these patients who stated that care was consistent with their preference to focus on comfort care than for those who wished to receive comfort care and stated that care was not consistent with their preference (38% vs 55% 1-year survival, P < .001). CONCLUSION: More than one in three seriously ill persons who prefer comfort care believe that their medical care is at odds with their preference that treatment focus on palliation. Such discord was associated with higher 1-year healthcare costs and increased survival.     

Morphometry of the anterior third ventricle region as a guide for the subfrontal (translaminaterminalis) approach

The anterior third ventricle region acquires clinical significance in benign and malignant tumors and cyst formations, of which craniopharyngiomas and gliomas are the most common. The subfrontal approach is one of the most preferred approaches for removing these tumors. In this study, the microsurgical anatomy of 81 Turkish, adult cadaveric hemispheres was examined to provide morphometric data of the region. These measurements from the anterior third ventricle region serve as a guide for neurosurgeons during surgical approach for removing anterior third ventricle tumors.     

Peritumoral brain edema in intracranial meningiomas evaluated by dynamic perfusion-weighted MR imaging: a preliminary study

Our objective was to semi-quantitatively evaluate the cerebral perfusion in the peritumoral brain edema of meningiomas using dynamic perfusion-weighted MR imaging. Six patients with intracranial meningiomas accompanied by peritumoral brain edema were prospectively examined by perfusion-weighted MR imaging. One patient was examined twice, once before and once 5 months after the surgical resection. The relative regional cerebral blood volume (rrCBV), the relative regional cerebral blood flow (rrCBF), and the relative regional mean transit time (rrMTT) were calculated for peritumoral brain edema and the contralateral white matter. These parameters were compared between peritumoral brain edema and the contralateral white matter. The time–concentration curve of the peritumoral brain edema was less prominent than that of the contralateral white matter, resulting in a significantly lower rrCBV (mean 46%) and rrCBF (mean 45%) in peritumoral brain edema than those of contralateral white matter. The serial perfusion-weighted MR imaging also demonstrated the recovery of these parameters after the removal of meningioma by means of surgical resection. Perfusion-weighted MR imaging can demonstrate significantly decreased rrCBV and rrCBF in peritumoral brain edema compared with those in normal white matter. Electronic Publication