Aerobic interval training attenuates remodelling and mitochondrial dysfunction in the post-infarction failing rat heart.

AIMS: Following a large myocardial infarction (MI), remaining viable muscle often undergoes pathological remodelling and progresses towards chronic heart failure. Mitochondria may also be affected by this process and, due to their functional importance, likely contribute to the progression of the disease. Aerobic interval training (AIT) has been shown effective in diminishing pathological myocardial transformation, but the effects of AIT on mitochondrial function in hearts undergoing remodelling are not known. METHODS AND RESULTS: Adult female Sprague-Dawley rats were randomized to either 8 weeks of aerobic interval treadmill running (5 days/week), which started 4 weeks after left coronary artery ligation (MI-Trained), or a sedentary group (MI-Sedentary). Echocardiography was performed before and after the 8-week period, at which point the left ventricles (LVs) were also harvested. Twelve weeks after surgery, MI-Sedentary rats had significantly lower LV fractional shortening compared with MI-Trained rats. Complex I-dependent respiration assessed in isolated LV mitochondria was decreased by ∼37% in MI-Sedentary and 17% in MI-Trained animals (group differences P < 0.05), compared with sham-operated animals. This was paralleled with diminished ATP production and increased degree of protein oxidation in MI-Sedentary rats. The enzymatic activity of complex I was also decreased to a greater extent in MI-Sedentary than in MI-Trained animals, with no evidence of its reduced expression. When complex II substrate was used, no differences among the three groups were observed. CONCLUSION: Exercise reduces LV contractile deterioration in post-infarction heart failure and alleviates the extent of mitochondrial dysfunction, which is paralleled with preserved complex I activity.

The effects of low-dose epinephrine infusion on spleen size, central and hepatic circulation and circulating platelets.

In several conditions associated with adrenergic stimulation, an increase in peripheral count of larger platelets has been observed, but the mechanism remained elusive. Larger platelets have greater prothrombotic potential and increase the risk of acute thrombotic events. The human spleen retains one-third of total body platelets, with mean volume (MPV) about 20% greater than that of circulating platelets. We aimed to answer whether low-dose epinephrine infusion results in spleen contraction and MPV increase. We undertook the continuous ultrasonic measurements of spleen volume, hepatic and central circulation with concurrent blood sampling in response to intravenous infusion of epinephrine (6 min of 0·06 µg kg(-1) per min, followed by 3 min of 0·12 µg kg(-1) per min) in nine healthy young subjects. The spleen volume started to decrease immediately after the onset of infusion, in the presence of substantial decreases in peripheral resistance and mean blood pressure and increases in heart rate and cardiac output. The majority of spleen emptying, approximately 25%, (95% CI 71·3-299·7) was observed 1 min after infusion onset, the hepatic vein flow peaked at the end of infusion for 28·4% (95% CI 1074·6-407·9), while increases in platelet count for approximately 31% (95% CI 187·8-314·8) and MPV for 4·4% (95% CI 7·3-10·9) lagged until 1 min after infusion cessation. We suggest that spleen is a dynamic reservoir of large platelets, which are mobilized even by low-dose epinephrine infusion in conditions of decreased blood pressure.

Cerebral oxygenation following epinephrine infusion.

Evidence suggests that the autonomic nervous system may actively regulate the cerebral vasculature. In this study, central hemodynamics and brain oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin changes (bO2Hb, bdHb and bTHb) were monitored during infusion of epinephrine (0.06 µg/kg/min over 6 min, and 0.12 µg/kg/min for 3 min) in 12 men. Epinephrine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and cardiac output (CO) increased, but did not affect bO2Hb, bdHb or bTHb. However, upon the cessation of epinephrine infusion an increase in both Oxy- and Total Hb occurred which peaked at 3 min post infusion (+6.0±4.6 and +4.9±4.8 µmol/L respectively, P<0.05) and persisted for 20 min post infusion (+1.5±2.2 and +1.8±2.7 µmol/L respectively, P<0.05). No evidence was found for reduction in cerebral oxygenation during a cold-pressor test. The results of the present study demonstrated that clinical doses of epinephrine result in a delayed increase in cortical blood volume due to an increase in Oxy-Hb, consistent with vasodilation.

Cardiovascular changes during underwater static and dynamic breath-hold dives in trained divers.

Limited information exists concerning arterial blood pressure (BP) changes in underwater breath-hold diving. Simulated chamber dives to 50 m of freshwater (mfw) reported very high levels of invasive BP in two divers during static apnea (SA), whereas a recent study using a noninvasive subaquatic sphygmomanometer reported unchanged or mildly increased values at 10 m SA dive. In this study we investigated underwater BP changes during not only SA but, for the first time, dynamic apnea (DA) and shortened (SHT) DA in 16 trained breath-hold divers. Measurements included BP (subaquatic sphygmomanometer), ECG, and pulse oxymetry (arterial oxygen saturation, SpO2, and heart rate). BP was measured during dry conditions, at surface fully immersed (SA), and at 2 mfw (DA and SHT DA), whereas ECG and pulse oxymetry were measured continuously. We have found significantly higher mean arterial pressure (MAP) values in SA (∼40%) vs. SHT DA (∼30%). Postapneic recovery of BP was slightly slower after SHT DA. Significantly higher BP gain (mmHg/duration of apnea in s) was found in SHT DA vs. SA. Furthermore, DA attempts resulted in faster desaturation vs. SA. In conclusion, we have found moderate increases in BP during SA, DA, and SHT DA. These cardiovascular changes during immersed SA and DA are in agreement with those reported for dry SA and DA.