Mechanisms Of Myocardial Energy Metabolic Disorders Responsible For Left Heart Failure Initiated By Lung Infection In Elderly Canines

ObjectivesTo study the mechanism of myocardial energy metabolic dysfunction in left heart insufficiency initiated by lung infection in elderly canines and to explore the warning state of LV function. Methods1. Set up of normal reference for LV function in elderly canines. 28 elderly canines, > 7 yrs of age, were catheterized to test LV Systolic Pressure Peak(LVSPP), the peak rate of pressure rise (+dp/dtmax), time to +dp/dt_max(t-dp/dt_max) ,LV End-Diastolic Pressure(LVEDP),the peak rate of pressure fall(-dp/dt_max),by which 95%confidence interval was to set up. 2. Cardiac insufficiency model produced by using percutaneous rapid right ventricular pacing and initially explore the turning point between compensated and decompensated heart failure .Seldinger technique was employed to puncture the jugular vein and VOO type of animal pacemaker were implanted with a pacing rate of 240bpm.3. Lung infection model produced by pseudomonas aeruginosa. A specially designed acute-hole jet device was employed to make the pseudomonas aeruginosa coated with alga acid in suspension with pseudomonas aeruginosa concentration of 9 x 10⁸cfu/ml and then 10ml suspension was dropped through the airway cannulation to the lung.72 hours later, the lung was harvested for histological study(HE stain) to confirm the successful infection.4. Study of Mechanisms of Myocardial Energy Metabolic Disorder Responsible for LV dysfunction initiated by Lung Infection in ElderlyCanines.Elderly canines were randomized to three groups ,of,pacing5d and pacing3d and then were continuously paced at 240bpm with VOO pacemaker for 7 days,5days and 3days, respectively. Control dogs were aslo implanted pacemaker without pacing.The pacemaker was turned off at the 7th ,5th and 3rd day and the same amount of pseudomonas aeruginosa were given to have the canine lung infected.LV function were tested before pacing, at pacer off and 3rd day after infection.Blood sample were obtained at Aorta and CS for difference analysis ,including blood glucose,FFA,lactate,PO2,PCO2.Lung were obtained for histological study to confirm the infection and also heart were harvested for electron microscopy study of left ventricle.The warning state of LV function was defined as the state of minimum +dp/dtmax and -dp/dttmax that with no LV failure after both pacing and lung infection.The 95% confidence interval(CI) of +dp/dtmax and -dp/dtmax was the intended warning interval for LV function. Results1. 95% confidence interval(95%CI) of parameters for LV function : LVSPP = 119-171 mmHg, +dp/dtmax = 2932 - 4354 mmHg/s, t-dp/dW =33-49 ms, LVEDP = -5-7mmHg, -dp/dtmax = 2202 - 3426 mmHg/s.2. As pacing continues,LV contractility and rexation gradually impaired. At 7th day,test were performed to all canines and only one was confirmed to have developed heart failure.Till nineth day after onset of pacing,there were all together 4 HF canines .3. Lung infection model created by pseudomonas aeruginosa . Three days later ,the lungs were harvested for histological study and the results showed alveolus edema and bleeding.Neutrophils were found assembled at around the alga-acid coated pseudomonas aeruginosa and bronchus-alveolus abscess formed. 4. Influence of pacing and lung infection on myocardial energy metabolism 4.1 Influence of rapid pacing on LV energy metabolism. No significiantchanges of myocardial energy metabolism were found.4.2 Influence of lung infection on myocardial energy metabolism: (l)group of pacing7d: the myocardial glucose consumption was markedly increased and at the same time the CS lactate level increased.However, no significant changes of tFFA consumption was observed.The O2 consumption was markedly decreased.Myocardial release of CO2 was not markedly decreased. (2) group of pacing5d:The myocardial glucose consumption was markedly increased.Meanwhile, the CS lactate level increased.However, no significant changes of tFFA consumption was observed.The O2 consumption was markedly decreased.Myocardial release of CO2 was slightly increased. (3) group of pacing3d: the myocardial glucose consumption was markedly increased and the the CS lactate level increased.However, no significant changes of tFFA consumption was observed.The O2 consumption was markedly decreased.Myocardial release of CO2 was not markedly decreased.4.3 LV mitochondria] injury by lung infection By electron microscopy study, LV mitochondrial injury or destroy was found.Mitochondrial profile changed and the ratio of length to width was decreased.Meanwhile, the inner mitochondrial membrane was injuried or destroyed with the ridge missing partially or totally.4.4 Warning state of LV function: +dp/dW=3500-3SOOmmHg/sj-dp/dtmax =2400-2900mmHg/s.Conclusions1. Elderly canine lung infection caused by pseudomonas aeruginosa impaired LV function and the onset of left heart failure is up to the LV function prior to lung infection.LV function below warning state predicts heart failure and that beyond warning state predicts no failure.2. There is no significant changes of myocardial metabolism of left ventricle by rapid right ventricle pacing for 7days, 5days and 3days respectively.3. Glycolysis system may not be injuried by lung infection.