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Background Survivors of a cardiac arrest often have persistent cardiovascular derangements following cardiopulmonary resuscitation including decreased cardiac output, arrhythmias and morphological myocardial damage. These cardiovascular derangements may lead to an increased susceptibility towards the external and internal environment of the cardiovascular system as compared to the healthy situation. Methods Here we tested the hypothesis that the cardiovascular system in healthy rats and rats resuscitated from a cardiac arrest may be differentially affected by a transient receptor potential vanilloid type 1 agonist, by continuous intravenous infusion of dihydrocapsaicin (DHC). Results Compared to baseline, infusion of DHC caused an initial increase in mean arterial blood pressure in both healthy and resuscitated rats of 25% and 10%, respectively. Also, we observed an initial response of tachycardia in both healthy and resuscitated rats of 30% and 20%, respectively. Then, at high levels of DHC infusion (> 2.0 mg/kg/hr) we observed two single episodes of transient bradycardia and hypotension in 33% of the healthy rats, which was consistent with a TRPV1 agonist induced Bezold-Jarisch reflex. In contrast, in resuscitated rats we observed multiple episodes of bradycardia/hypotension in 100% of the rats and at a dose of DHC of 0.65 mg/kg/hr. Notably, this DHC effect could be completely blocked in the resuscitated rats by pre-treatment with atropine, a muscarinic acetylcholine antagonist. Conclusions Our results indicate that the susceptibility of the rats towards TRPV1 agonist induced Bezold-Jarisch reflex is increased in those resuscitated from cardiac arrest compared to the healthy situation.

The Nordic Cooling Stroke Study (NOCSS) is a multicenter, multinational, randomized, controlled trial investigating the possible neuroprotective efficacy of induced mild hypothermia in acute stroke patients. Cerebral computed tomography scans are performed to exclude hemorrhages, tumors, and other causes simulating the symptoms of an ischemic stroke. The cooling procedure is initiated within 6 h of onset of symptoms and active cooling persists for 9 h, resulting in an average of 12 h of hypothermia. The rewarming is passive. The target temperature is 35°C (deep rectal) and the method of inducing hypothermia is surface cooling using the Arctic Sun (model 200, Medivance, Louisville, CO, USA). The method of inducing hypothermia is deliberately noninvasive and the patients are, moreover, nonanesthetized in order to offer a study design that can be implemented easily and potentially benefit a large percentage of the stroke population.

Summary Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature is directly related to stroke severity and outcome, and fever after stroke is associated with substantial increases in morbidity and mortality. Normalisation of temperature in acute stroke by antipyretics is generally recommended, although there is no direct evidence to support this treatment. Despite its obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects— such as hypotension, cardiac arrhythmia, and pneumonia—it is still thought of as experimental, and evidence of efficacy from clinical trials is needed.

Infection is a frequent complication in the early course of acute stroke and may adversely affect stroke outcome. In the present study, we investigate early infection developing in patients within 3 days of admission to the hospital and its independent relation to recovery and stroke outcome. In addition, we identify predictors for early infections, infection subtypes, and their relation to initial stroke severity.In the community-based Copenhagen Stroke Study, 1,156 unselected patients were examined for early infection. Stroke severity was assessed with the Scandinavian Stroke Scale (SSS) on admission and at discharge. Multiple logistic and linear regression analyses were used to determine independent relations to early infection. Relevant stroke risk factors, admission stroke severity, and body temperature were included in the analysis.Of the subjects studied, 19.4% developed early infection. In women, 68% of the early infections were urinary tract infections, and in men, 49% of the early infections were pneumonias. Independent predictors of early infection were advanced age (OR per 10 years, 1.24; 95% CI, 1.02-1.64), female gender (OR, 2.0; 95% CI, 1.3-3.0), and decreased SSS score on admission (OR per 10 points, 0.69; 95% CI, 0.62-0.78). The presence of early infection prolonged hospital stay by a mean of 9.3 days (P.0001) but not death during hospital stay (P = .78), stroke severity at discharge (P = .32), or rate of discharge to nursing home (P = .17).Advanced age, female gender, and increased stroke severity independently predict development of early infection. The present study indicates that early infection does not influence outcome in acute stroke patients per se, but it delays patient discharge from the hospital.

Background The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion. Results Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Conclusions Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia.