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: Therapeutic hypothermia has been shown to reduce brain damage due to postcardiac arrest syndrome. Actually, there is no agreement on which is the best device to perform therapeutic hypothermia. The 'ideal' device should not only 'cool' patient until 33-34°C as fast as possible, but also maintain the target temperature and reverse the therapeutic hypothermia. For out-of-hospital cardiac arrest, there are devices that allow starting of therapeutic hypothermia on the field (prehospital hypothermia). On hospital arrival, these prehospital devices can be quickly and easily replaced with other devices more suitable for the management of therapeutic hypothermia in ICUs (in-hospital hypothermia). Some studies have compared surface and endovascular devices and found no substantial differences in neurologic outcome or survival at hospital discharge. On a clinical ground, the knowledge of the technical aspects of therapeutic hypothermia (such as characteristics of devices) is mandatory for clinicians who have to perform therapeutic hypothermia in cardiac arrest patients because the timing of therapeutic hypothermia, the choice of the device for the single patients, and avoidance of temperature fluctuation have shown to affect outcome in these patients (also in terms of reducing the incidence of complications).

Objective: Beta1- and beta2-adrenergic receptors (ARs) play a pivotal role in myocardial function. We investigated whether functionally relevant polymorphisms within the genes encoding for these receptors indicate susceptibility to idiopathic dilated cardiomyopathy (DCM)., Methods: This case-control association study involved 189 patients with DCM and 378 gender- and age-matched control subjects. All of the subjects were characterised by polymerase chain reaction-restriction fragment length polymorphism analysis in terms of Ser49Gly and Arg389Gly polymorphisms in the beta1-AR, and the 5' leader cistron Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in the beta2-AR. Genotype, allele and haplotype frequencies were analysed., Results: Univariate analysis showed that the distribution of genotype and allele frequencies of the beta1-Ser49Gly, beta1-Arg389Gly and beta2-Arg16Gly polymorphisms was significantly different between the patients and controls, and the beta1-Gly49/beta1-Arg389 haplotype was significantly more represented in the patients. Multivariate analysis showed that only the beta1-Gly49 variant (odds ratio 1.91; 95% confidence interval 1.24-2.95; P = 0.003) and beta2-Gly16Gly genotype (odds ratio 1.58; 95% confidence interval 1.10-2.26; P = 0.013) carriers were at significantly higher risk of developing DCM., Conclusions: In our population from southern Italy, the Gly49 allele of the beta1-AR and the Gly16Gly genotype of the beta2-AR were significantly and independently associated with the DCM phenotype, thus suggesting their role in favouring susceptibility to the disease.

Background: The offspring of hypertensive families are characterized by higher arterial blood pressure values and a depressed autonomic control of heart rate. The present study aimed to verify whether these differences are associated with a different genotype distribution of functionally relevant polymorphisms of the alpha- and beta-adrenergic receptor (AR) genes., Methods: We selected 109 age- and sex-matched young normotensive subjects with (FH+, n = 56) and without (FH-, n = 53) a family history of hypertension who underwent evaluation of arterial pressure; 24-h electrocardiogram monitoring to assess time-domain parameters of autonomic heart rate control [i.e. mean RR interval (NN), SD of RR intervals (SDNN) and mean square root of the differences of consecutive RR intervals (rMSSD)]; spectral baroreflex sensitivity measurement; and echo-Doppler to assess diastolic function and left ventricular mass. They were also characterized for the following polymorphisms by means of polymerase chain reaction-restriction fragment polymorphism analysis: Arg492Cys in the alpha1a-AR; Del301-303 in the alpha2b-AR; Ser49Gly and Arg389Gly in the beta1-AR; and the 5' leader cistron Arg19Cys, Arg16Gly and Gln27Glu in the beta2-AR., Results: FH+ individuals showed a higher systolic pressure, a lower SDNN and a greater isovolumic relaxation time compared to normotensive offspring. No differences were found between the two groups when genotype distribution of the studied polymorphisms was considered. Subjects carrying alpha1a-AR Cys492 allelic variant showed lower values of NN, SDNN and rMSSD, independent of age, gender and body mass index., Conclusions: The functionally relevant polymorphisms of alpha2b-, beta1- and beta2-AR genes are not associated with a family history of essential hypertension. The Arg492Cys polymorphism of the alpha1a-AR gene, although not associated with a family history of hypertension, was strongly related to autonomic control of heart rate.

In the kidney, angiotensin-(1-7) [Ang-(1-7)] exhibits diuretic and natriuretic properties associated with an increase in prostaglandin production. The prohypertensive effects of Ang II are attenuated in rats infused with Ang-(1-7), consistent with recent work showing that Ang-(1-7) downregulates AT1 receptors in Chinese hamster ovary-AT1A or vascular smooth muscle cells. To determine whether exposure to Ang-(1-7) reduces AT1 receptors in the kidney through an increase in prostaglandin production, kidney slices from Sprague-Dawley rats were incubated with 10 n -1 microM Ang-(1-7) in the presence or absence of 5 microM meclofenamate, a cyclooxygenase inhibitor. Following these treatments, the kidney slices were retrieved, frozen, and sectioned for determination of [125I]-Ang II binding using in vitro receptor autoradiography. Greater than 90% of the specific binding was competed for by losartan, indicating that the majority of binding was to the AT1 receptor. Incubation of kidney slices with 1 microM Ang-(1-7) caused a 20% reduction in [125I]-Ang II binding (n = 8) in the cortical tubulointerstitium, which was prevented when Ang-(1-7)-treated slices were incubated in the presence of 5 microM meclofenamate (1 +/- 2% increase, n = 8; p < 0.05). Incubation with 5 microM meclofenamate alone had no effect on [125I]-Ang II binding (-3 +/- 3%). The decrease in [125I]-Ang II binding with Ang-(1-7) was also blocked by the Ang-(1-7) antagonist [d-Ala7]-Ang-(1-7). Treatment with 1 microM [d-Ala7]-Ang-(1-7) alone had no effect on [125I]-Ang II binding (-3 +/- 6% of control). Pretreatment with 1 microM Ang II caused a similar reduction in [125I]-Ang II binding in the cortical tubulointerstitium. Neither Ang-(1-7) nor Ang II had any effect on [125I]-Ang II binding in the glomeruli and the area of the vasa recta of the kidney. These original findings suggest that prior exposure to Ang-(1-7) or Ang II causes a modest decrease in the number of AT1 receptors in the cortical tubulointerstitial area of the kidney. The reduction in Ang II binding by Ang-(1-7) was blocked by meclofenamate and [d-Ala7]-Ang-(1-7), suggesting that cyclooxygenase products released through activation of a novel receptor participate in this effect.

Background: Intrathecal neostigmine may produce analgesia by itself and may enhance analgesia from spinal clonidine. Before clinical trials, the spinal cord blood flow effects of these drugs alone and in combination should be examined in animals., Methods: Conscious, nonpregnant ewes with indwelling vascular and thoracic spinal catheters received intrathecal injection of 0.2 or 2 mg neostigmine, 0.2 mg clonidine, or 2 mg neostigmine plus 0.2 mg clonidine. Mean systemic and pulmonary arterial and central venous pressures, heart rate, and cardiac output were monitored, arterial blood was sampled for blood gas tensions and pH, and spinal cord blood flow was determined by colored microsphere injection before and at 15, 60, and 240 min after spinal study drug injection., Results: Neostigmine alone did not affect cardiorespiratory variables or spinal cord blood flow. Intrathecal clonidine alone decreased systemic arterial and central venous pressures, whereas these effects were not observed with addition of neostigmine. Clonidine or neostigmine alone or the combination of clonidine and neostigmine did not affect spinal cord blood flow., Conclusions: Intrathecal neostigmine alone or in combination with clonidine does not reduce spinal cord blood flow, an important preclinical toxicity issue. These results provide additional support for initial clinical trials of intrathecal neostigmine for analgesia.

The effects of ULFS-49, a new calcium channel blocker, on right ventricular (RV) systolic and diastolic performance were evaluated in nine anesthetized, closed-chest dogs by load-insensitive indexes. ULFS-49 (0.3 mg/kg) decreased heart rate (HR) from 76 +/- 25 to 47 +/- 11 beats/min (p less than 0.01) and cardiac output (CO) from 1.89 +/- 0.62 to 1.42 +/- 0.72 L/min (p less than 0.01), as RV free wall end-diastolic area increased from 486 +/- 126 to 581 +/- 45 mm2 (p less than 0.01) and RV end-diastolic volume increased from 66.6 +/- 26.4 to 85.3 +/- 28.5 ml (p less than 0.05). Pacing at 100 beats/min ablated these hemodynamic and dimensional changes. RV free wall contractility was assessed by the slope and midrange intercept values of the relation between RV end-systolic pressure (Pes) and end-systolic free wall area (Aes) and between RV free wall segmental work (SW) and end-diastolic area (Aed). RV free wall stiffness was measured by exponential fit of the RV end-diastolic pressure (Ped)-Aed points during caval occlusion. With pacing at 100 beats/min, the slope of the Pes-Aes relationship was unchanged by ULFS-49 (0.52 +/- 0.29 vs. 0.60 +/- 0.35 mm Hg/mm2) as was the midrange intercept (382.3 +/- 114.7 vs. 387.1 +/- 121.5 mm2). After administration of ULFS-49, the slope of the SW-Aed relation increased from 31.8 +/- 14.4 to 37.3 +/- 17.7 mm Hg.mm2 (p less than 0.05) without changing the midrange intercept (410.5 +/- 108.1 mm2 vs. 413.0 +/- 107.0 mm2). Similarly, neither the position nor curvature of the Ped-Aed relation was changed by ULFS-49. These data demonstrate that ULFS-49 causes significant bradycardia and increases the size of the right ventricle without directly depressing RV free wall systolic or diastolic performance.

Increasing the ratio of tissue oxygen delivery (DO2) to oxygen consumption can improve the survival of critically ill patients, including those with acute respiratory failure. However, under conditions of ventilation/perfusion mismatch, the use of inotropic or vasodilator drugs to augment cardiac output could, in turn, worsen venous admixture. In a canine model of asymmetric oleic acid-induced pulmonary edema, we examined this possibility by studying the effect of 20 and 40-micrograms/kg doses of parenteral nifedipine on oxygenation variables, venous admixture, and intrapulmonary blood flow distribution. After oleic acid injury, nifedipine caused significant increases in cardiac index by 70% as systemic vascular resistance decreased proportionately by 61%. Stroke volume index (SI) and mean pulmonary arterial pressure increased, while venous admixture and the distribution of intrapulmonary blood flow did not change with nifedipine. However, nifedipine significantly improved the tissue DO2 index so that the coefficient of DO2 increased. Thus, nifedipine significantly increased SI in a dose-dependent manner, thereby improving the tissue oxygen supply-demand balance.

The hypoxic pulmonary vasoconstrictive (HPV) response is characterized by two components: intrapulmonary blood flow redistribution and pulmonary artery pressure (PAP) augmentation. Whether both remain intact after oleic acid lung injury has not been assessed. In an asymmetric model of right lung oleic acid edema, we examined the relative magnitude of each component on the HPV response to right lung inspired hypoxia. Before oleic acid administration, right lung hypoxia decreased perfusion to the right lung from 1.41 +/- 0.12 to 1.16 +/- 0.15 L/min (p = .07), while PAP increased from 15.8 +/- 0.8 to 18.1 +/- 0.6 mm Hg (p less than .05). Regional hypoxia caused right lung pulmonary vascular resistance (PVR) to increase from 480 +/- 45 to 797 +/- 114 dyne.sec/cm5 (p less than .01). After right lung injury with oleic acid, regional hypoxia decreased perfusion to the right lung from 0.91 +/- 0.11 to 0.71 +/- 0.10 L/min (p less than .05), while PAP increased from 18.8 +/- 0.8 to 21.5 +/- 1.0 mm Hg (p less than .05). With hypoxia, right lung PVR increased from 1232 +/- 260 to 1933 +/- 336 dyne.sec/cm5 (p less than .01). We conclude that the pulmonary vasoconstrictive response to inspired hypoxia persists after oleic acid lung injury, causing significant increases in PVR. Consequently, both the blood flow redistribution and the PAP augmentation components of the HPV response to inspired hypoxia remain unchanged.

The effects of PEEP and subsequent augmentation of cardiac output by sodium nitroprusside (SNP) were examined in a canine model of asymmetric oleic acid injury to the right lung. PEEP (9.2 +/- 0.5 cm H2O) was added to six animals to decrease venous admixture (Qsp/Qt) from 50.6 +/- 4.4% to 16.0 +/- 1.3% (p less than .05). With PEEP, intrapulmonary blood flow distribution (assessed by radioactive microspheres) decreased significantly to nondependent lung regions while increasing to dependent regions. In six other animals, zero end-expiratory pressure (ZEEP) did not alter intrapulmonary blood flow distribution. SNP was then administered to increase cardiac output by 40% (to 2.60 +/- 0.21 L/min in the ZEEP group and to 1.75 +/- 0.27 L/min in the PEEP group). SNP produced no adverse effects on Qsp/Qt or intrapulmonary blood flow distribution. Specifically, SNP did not preferentially dilate pulmonary vessels injured by oleic acid with or without end-expiratory pressure. Thus, administration of a vasodilator drug in asymmetric pulmonary edema appears well tolerated.