Hemodynamic modifications induced by hypoxia in the dog]

In non hypercapnic hypoxia (inhalation of a 4,5% O2 mixture during 10 minutes) blood pressure, heart rate, cardiac output, femoral and carotid blood flow inhance so that, in less extent, vertebral blood flow. Such a reaction is consequent with an hypoxic stimulation of adrenal glands.     

Intensive statin therapy in acute coronary syndromes: clinical benefits and vascular biology

PURPOSE OF REVIEW: The results of a landmark clinical study comparing intensive statin therapy with conventional statin therapy, in patients with acute coronary syndromes (ACS), are reviewed. The mechanisms behind these results are analysed drawing data from vascular and cell biology. RECENT FINDINGS: The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) study showed that intensive statin therapy with 80 mg of atorvastatin to achieve a low-density lipoprotein cholesterol of 62 mg/dl resulted in a 3.9% absolute and a 16% relative risk reduction in death or major cardiovascular events up to 2 years, compared to 40 mg of pravastatin, in patients with ACS. The results were especially significant as intensive statin therapy resulted in a very early benefit (<30 days) and occurred against a background of percutaneous coronary intervention (69%) for the index admission and high use of medications for secondary prevention. The PROVE IT and the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) C-reactive protein sub-study also showed that atorvastatin (80 mg) resulted in a significant reduction in markers of inflammation, whilst the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study showed that intensive statin therapy was associated with reduced progression of atherosclerosis compared with conventional doses of statins. SUMMARY: Intensive statin therapy results in a significant early reduction in adverse cardiac events in ACS patients which are sustained over 2 years. The early benefits seen are likely to result from modulation of inflammation, endothelial function and coagulation, i.e. the pleiotropic effects, whereas the greater reduction in low-density lipoprotein cholesterol results in reduced long-term events.     

Serotonin and 5-hydroxyindolacetate during acute renal ischemia]

During the acute renal ischemia (lasting up to 24 hrs) in rabbits the serotonin level displayed similar changes in the ischemic and contralateral kidney. In the tissues under study serotonin decreased during the first fifteen minutes of ischemia; then a tendency to increase with a maximal rise in the ischemic kidney after a 60-min ischemia was seen; as to the contralateral kidney--the maximal rise occurred after a 3 hr ischemia. At the further stages of ischemia serotonin content fell again, particularly in the ischemic kidney. The blood serotonin level increased somewhat during the 60-min ischemia. An increase in the 5-hydroxyindolacetate concentration in the urine coincided with the period of decrease of the tissue serotonin content.     

Thrombolytic therapy in arterial thrombosis producing acute ischemia of the lower limbs]

Efficiency of the thrombolytic therapy in the acute arterial thrombosis (producing an acute ischemia of the lower limbs) with streptokinase has been assessed in 35 patients treated in the selected departments of vascular surgery in Poland. Complete recovery has been noted in 9 patients (25.7%) in whom limb functioning with detectable peripheral pulse have been restored. An improvement has been achieved in 12 (34.3%) patients and moderate result in 4 (11.4%) patients. The limb has been amputated in 7 (20%) patients, and 3 patients (8.6%) died. Similar results have been observed in case of ischemia of duration period below 12 hours, between 12 and 24 hours, and between 24 and 72 hours. The results have been worse when thrombolytic therapy was introduced after 72 hours.     

Excitation-contraction uncoupling during ischemia in the blood perfused dog heart

The bioluminescent of Ca(2+)-indicator, aequorin, was loaded into the left ventricular apex of blood-perfused hearts from 13 dogs for simultaneous recording of left ventricular pressure and intracellular calcium levels. During a 2 minute period of ischemia, systolic and diastolic pressures significantly decreased. In contrast, these pressure changes were associated with an increase in both systolic and diastolic calcium reaching a maximum diastolic value of 0.59 microM and a systolic value of 1.11 microM. This apparent dissociation between pressure and [Ca2+]i supports the hypothesis that changes in myofilament Ca2+ responsiveness are of major importance in modulating contractility during ischemia in large mammalian hearts.     

Cholinergic enzyme activity during partial brain ischemia in the dog

Activity of cholinacetyltransferase (ChAT. EC 2.3.1.6) and acetylcholinesterase (AChE, EC 3.1.1.7) was monitored during occlusion of arteria cerebri media dx. (MCA) in five areas of the brain cortex, in nucleus caudatus and in the thalamus of the ipsilateral and contralateral hemisphere. After 1 hour of MCA occlusion ChAT and AChE activity was reduced in the ischemised region of the hemisphere, i. e. in gyrus ectosylvius anterior and gyrus sylvius anterior, whereas after 4 hours of occlusion the differences were not significant. In nc. caudatus and thalamus the activity of enzymes during ischemia did not change much.     

The effect of acute ischemia on the small intestine of the dog

There were carried out macroscopic and microscopic observations of dog's small intestine after putting a clamp on the artery only or on the artery and the upper mesenteric vein. Examinations were performed after 1 and 2 h of ischemia and in different periods after restitution of circulation. By means of histologic and histochemical methods it was found out that no later than after 1 h of ischemia there occur pathologic, irreversible changes in the wall of the small intestine.     

Renal metabolism and ammoniagenesis during acute respiratory alkalosis in the dog

Acute respiratory alkalosis (blood pH, 7.60; arterial PCO2, 15 mmHg (1 mmHg = 133.322 Pa); plasma bicarbonate, 14 mM) was induced in nine anesthetized dogs by increasing their respiratory rate and depth. Renal glutamine extraction and ammonia production expressed per 100 mL of glomerular filtration rate did not change during acute hypocapnia, whereas arterial glutamine concentration decreased significantly from 0.47 to 0.36 mM. Hypocapnia did not change plasma potassium concentration and its urinary excretion. Acute hypocapnia increased lactate extraction and pyruvate production, whereas citrate extraction and glutamate and alanine production did not change. Citraturia remained minimal. Renal cortical glutamine concentration fell from 0.64 to 0.38 mM during hypocapnia while alpha-ketoglutarate, glutamate, malate, oxaloacetate, and citrate did not change. Lactate concentration rose from 1.1 to 2.0 mM. Glutamine concentration in the liver and muscle decreased following acute hypocapnia. Our data are compatible with the hypothesis that an acute respiratory alkalosis might not result in any change in the hydrogen ion concentration and (or) gradient between the mitochondrial matrix and the cytosol. Consequently, renal glutamine extraction and ammonia production are not reduced, renal cortical concentrations of relevant metabolites in the ammoniagenic pathway are not changed, and renal handling of citrate remains unaffected.     

Increased propensity for apnea in response to acute elevations in left atrial pressure during sleep in the dog.

Periodic breathing is commonly observed in chronic heart failure (CHF) when pulmonary capillary wedge pressure is abnormally high and there is usually concomitant tachypneic hyperventilation. We hypothesized that acute pulmonary hypertension at pressures encountered in CHF and involving all of the lungs and pulmonary vessels would predispose to apnea/unstable breathing during sleep. We tested this in a chronically instrumented, unanesthetized dog model during non-rapid eye movement (NREM) sleep. Pulmonary hypertension was created by partial occlusion of the left atrium by means of an implanted balloon catheter in the atrial lumen. Raising mean left atrial pressure by 5.7 +/- 1.1 Torr resulted immediately in tachypneic hyperventilation [breathing frequency increased significantly from 13.8 to 19.9 breaths/min; end-tidal P(CO2) (P(ET(CO2))) fell significantly from 38.5 to 35.9 Torr]. This tachypneic hyperventilation was present during wakefulness, NREM sleep, and rapid eye movement sleep. In NREM sleep, this increase in left atrial pressure increased the gain of the ventilatory response to CO2 below eupnea (1.3 to 2.2 l.min(-1).Torr(-1)) and thereby narrowed the CO2 reserve [P(ET(CO2)) (apneic threshold) - P(ET(CO2)) (eupnea)], despite the decreased plant gain resulting from the hyperventilation. We conclude that acute pulmonary hypertension during sleep results in a narrowed CO2 reserve and thus predisposes toward apnea/unstable breathing and may, therefore, contribute to the breathing instability observed in CHF.