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The Cardiac Profile, a pattern of serum enzyme changes seen within seventy-two hours after an AMI, is diagnostic aid for detecting occurrence of infarcts. The effects of exercise stress on the Cardiac Profile aid clinicians in avoiding diagnostic errors in patients immediately after exercise. Five male volunteers ran from six to ten miles. Serum enzyme levels were monitored serially three days before and five days after stress. Enzyme activity was determined spectrophotometrically and electrophoretically. Significant increases in total CPK and LDH were seen. An LDH 'one-two flip' occurred eight hours after exercise. No MB-CPK was found following the run.

Wang Mei. / "July 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 208-233). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Proper heart function results from the periodic execution of a series of coordinated interdependent mechanical, chemical, and electrical processes within the cardiac tissue. Central to these processes is the action potential - the electrochemical event that initiates contraction of the individual cardiac myocytes. Many models of the cardiac action potential exist with varying levels of complexity, but none account for the electrophysiological role played by caveolae - small invaginations of the cardiac cell plasma membrane. Recent electrophysiological studies regarding these microdomains reveal that cardiac caveolae function as reservoirs of 'recruitable' sodium ion channels. As such, caveolar channels constitute a substantial and previously unrecognized source of sodium current that can significantly influence action potential morphology. In this thesis, I formulate and analyze new models of cardiac action potential which account for these caveolar sodium currents and provide a computational venue in which to develop and test new hypotheses. My results provide insight into the role played by caveolar ionic currents in regulating the electrodynamics of cardiac myocytes and suggest that in certain pathological cases, caveolae may play an arrhythmogenic role.

Background: Loading conditions are recognized to influence ventricular function according to the Starling relationship for length/stretch and force.  Many modern echocardiographic parameters which have been announced as describing ventricular function and contractile status, may be confounded by uncontrolled and unmeasured load.  These studies aimed to measure the relation between four differ­ent types of assessments of ventricular dysfunction and degrees of load.  Study examined the ‘myo­cardial performance index’ (MPI).  Study II examined long axis segmental mechanical dyssynchrony.  Study III examined tissue velocities, and Study IV examined ventricular twist.  All studies aimed to describe the relation of these parameters both to load and to inotropic changes. Methods:  In anesthetized juvenile pigs, left ventricular (LV) pressure and volume were measured continuously and their relationship (LVPVR) was analysed.  Preload alterations were brought about by inflation of a balloon tipped catheter in the inferior vena cava (IVCBO).  Inotropic interventions were brought about by either an overdose of anesthetic (combine intravenous pentobarbital and inhaled isoflurane, Study I), or beta blocker and calcium channel blocker given in combination (Stud­ies III and IV).  In one study (II), global myocardial injury and dysfunction was induced by endotoxin infusion.  MPI measurements were derived from LVPVR heart cycle intervals for isovolumic contrac­tion and relaxation as well as ejection time.  Long axis segmental dyssynchrony was derived by ana­lyzing for internal flow and time with segmental dyssynchronous segment volume change during systole, hourly before and during 3 hours of endotoxin infusion.  Myocardial tissue velocities were measured during IVCBO at control, during positive and then later negative inotropic interventions.  The same for apical and base circumferential rotational velocities by speckle tracking.  Load markers (including end-diastolic volume) were identified for each beat, and the test parameters were analysed together with load for a relation.  The test parameters were also tested during single apneic beats for a relation to inotropic interventions. Results: MPI demonstrated a strong and linear relationship to both preload and after-load, and this was due to changes in ejection time, and not the isovolumic intervals.  Long axis segmental dyssyn­chrony increased during each hour of endotoxin infusion and global myocardial injury.  This dysyn­chrony parameter was independent of load when tested by IVCBO. Peak systolic velocities were strongly load-independent, though not in all the inotropic situations and by all measurement axes.  Peak systolic strain was load-dependent, and not strongly related to inotropic conditions.  Peak sys­tolic LV twist and untwist were strongly load-dependent. Conclusions: MPI is strongly load-dependent, and can vary widely in value for the same contractile status if the load is varied.  Mechanical dyssynchrony measures are load-independen in health and also in early global endotoxin myocardial injury and dysfunction.  Peak sytole velocities are a clinically robust parameter of LV regional and global performance under changing load, though peak systolic strain seems to be load-dependent.  Left ventricular twist and untwist are load-dependent in this pig model.

This thesis describes the development of MRI techniques for identifying disease within cardiac muscle of the rodent heart at 4.7 T. The new methods allow measurement of myocardial T1 and T2* relaxation times and ventricular volumes from cine images. Before in-vivo application, each MRI pulse sequence and imaging protocol was tested using tissue representative phantoms on a cardiac motion simulator. A multi-slice cardiac cine pulse sequence was developed for measuring cardiac volumes that used a modified slice acquisition order compared to standard cine MRI to extend TR and thereby increase the signal without extending the total scan time. This acquisition method was compared to a slower conventional cine pulse sequence by measuring the signal to noise ratio and the left ventricular mass and volumes of the mouse heart. T1 values are known to increase in hearts affected by dilated and hypertrophic cardiomyopathy, so pulse sequences were developed for measuring myocardial relaxation values. In-vivo T1 measurements were made using saturation and inversion recovery pulse sequences. Comparison of the results showed that the inversion recovery pulse sequence gave results that were more consistent with published values from similar studies so it was concluded that this should be used for future cardiomyopathy investigations. A study was carried out on an in-vivo control group to test the effectiveness of the superparamagnetic contrast agent Ferumoxytol in enhancing T2* differences between healthy and pathological tissues. It was found that Ferumoxytol did not affect the T2* of the healthy myocardium and this result was confirmed by histology which revealed very little Ferumoxytol uptake in the heart but plentiful uptake in the liver. The results of this study indicate that future investigations in rats with induced cardiomyopathy can assume that changes in myocardial relaxation times are due to the effects of cardiac disease rather than the contrast agent.

Ischemic heart disease represents a leading cause of death worldwide. Ischemia denotes an insufficient supply of oxygenated blood to the heart due to occlusion of the coronary vessels. Timely reperfusion, i.e., restoring blood flow to the ischemic part of the heart, limits ischemic damage. However, reperfusion itself induces injury to the heart. This phenomenon is referred as ischemia/reperfusion (I/R) injury. Osteopontin (OPN), also known as cytokine Eta-1, is a cell-secreted extracellular matrix protein. Expression of OPN increases in the heart in response to a variety of pathological conditions. Mice lacking OPN exhibit exaggerated left ventricular dilation in non-reperfused model of myocardial remodeling. Cardioprotective role of OPN has also been demonstrated in a mouse model of repetitive I/R injury for 7 days. The objective of this study was to examine the role of OPN in modulation of systolic and diastolic parameters of the heart following I/R injury in a time-dependent manner. For this study, wild type (WT) and OPN knockout (KO) mice aged ~4 months were subjected to cardiac ischemia by the ligation of left anterior descending coronary artery (LAD). Following 45 min of ischemia, the LAD was reperfused by snipping the ligature. Heart function was measured using echocardiography at baseline, 3, 7, 14, and 27 days following I/R injury. M-mode echocardiographic images were used to calculate the systolic parameters (% fractional shortening [%FS], % ejection fraction [%EF], and end-systolic volume [ESV]), while pulse wave Doppler images were used to calculate diastolic parameter (aortic ejection time; [AET]). Global cardiac function was evaluated using myocardial performance index (MPI; a Doppler-derived index which combines systolic and diastolic functions). At basal levels, most of the systolic and diastolic parameters remained unchanged between the two groups. I/R injury decreased %FS and EF in both groups vs the baseline values at 3, 7, 14 and 27 days post-I/R. However, the decrease in %FS and EF was significantly greater in KO-I/R vs WT-I/R group. ESV was significantly higher in WT mice 7 days post-I/R, and stayed higher 14 and 27 days post-I/R vs baseline. However, the increase in ESV was significantly greater in KO mice 3 day post-I/R, and remained higher vs WT-I/R during the time course. AET was lower in WT group 14 days post-I/R vs baseline. On the other hand, AET was significantly lower in KO group 3, 7, 14 and 27 days post-I/R vs WT-I/R. MPI was higher in WT group 7 days post-IR vs baseline. MPI decreased significantly in WT group 27 days vs 7 days post-I/R. In KO group, MPI was significantly higher than WT mice at baseline, and remained higher 3 and 27 day post-I/R vs WT-I/R. Thus, lack of OPN decreases systolic and diastolic functional parameters of the heart following I/R injury, suggesting a cardioprotective role of OPN in myocardial remodeling post-IR.

This study sought to examine the exercise-induced ST-segment shifts, J₀ and J₆₀, attributable to ECG lead configuration, specifically to evaluate if ischemic changes are modified as a function of using the Mason-Likar lead system. Males (N=30) referred for diagnostic testing underwent a symptom-limited graded exercise test (SLGXT). ST-segment shifts, J₀ and J₆₀, measured as the difference from baseline to recovery minute one, were not significantly different in responses measured from two simultaneous complexes for lead V₅. In frontal lead II, differences were found in the ST-segment response at baseline vs. recovery minute one. All ST-segment shifts were computed as the difference between J_x obtained at resting baseline vs. the J_x obtained at the exercise measurement in the same posture. ST-segment shifts, J₀ and J₆₀, measured at peak-exercise vs. recovery minute one using the Mason-Likar lead system, revealed a significant difference according to the measurement recorded in both leads V₅ and II (p<.05). Comparisons of frequencies for clinically abnormal ST-segment shifts according to ECG lead configuration at recovery minute one when measured from peak-exercise using Mason-Likar were significant in only lead II (p<.05). Observation of the data suggest that the Mason-Likar lead system may affect the interpretation of ischemic ST-segment shifts in lead II. However, these results do not invalidate the interpretation of ischemic ST-segment shifts in lead V₅ using the Mason-Likar lead system. / Master of Science

Acute myocardial infarction occurs when there is reduced blood supply to the myocardium promoting decrease of oxygen uptake (O2). It is a major cause of morbidity and mortality worldwide. Tissue injury occurs, for the most part, paradoxically, during reperfusion of the organ. In reoxygenation, there are exacerbated production of reactive oxygen species (ROS) and intracellular calcium overload, which trigger cell death. There are few pharmacological intervention strategies for the prevention and limitation of these lesions. And besides, the available forms of action are not entirely effective. Recently, it has directed attention to the effects of natural products in limiting the damage caused by ischemia and reperfusion (I/R). In this context, thymol, a phenolic monoterpene, has, among its biological activities, anti-inflammatory and antioxidant. In this sense, the objective of the study was to evaluate the potential cardioprotective effect of thymol in preventing reperfusion injury after ischemia in rats. First it performed the test clearance of radical DPPH by thymol. To study its potential cardioprotective, rats Wistar rats (200-300 g) pretreated with thymol (7.5 mg/kg, v.o.) or vehicle for 7 days and subjected to global ischemia of the heart in the Langendorff system. We evaluated parameters of cardiac function as left ventricle developed pressure (LVDP), maximum time derivative (+ dP/dt) and minimum (-dp/dt) and arrhythmia severity index (ASI), size of the infarcted area, and enzymatic activity assays catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and reductase (GR), tissue sulfhydryl quantification. Moreover, the concentration of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides evaluated too. The DPPH assay showed antioxidant property of thymol. Furthermore, it was observed that pretreatment with thymol preserved LVDP, ASI decreased, reduced infarct area, the TBARS and, similarly, was observed lower concentration of hydroperoxides as compared to vehicle. Pretreatment with thymol prevented to reduce the concentration of sulfhydryl groups when compared to vehicle. The activities of SOD, CAT, GPx and GR were reduced significantly in the hearts of animals pretreated with thymol when compared to vehicle. Pretreatment with thymol preserved contractile heart function, reduced damage to cellular components and limited the infarct area. Demonstrating significant cardioprotective effects against I/R. / O infarto agudo do miocárdio ocorre quando há diminuição do suprimento sanguíneo no miocárdio promovendo queda do aporte de Oxigênio (O2). É uma das principais causas de morbidade e mortalidade em todo o mundo. A lesão tecidual ocorre, em sua maior parte, paradoxalmente, durante a reperfusão do órgão. Na reoxigenação, há exacerbada produção de espécies reativas de oxigênio (EROs) e sobrecarga de cálcio intracelular, que desencadeiam a morte celular. Poucas são as estratégias de intervenção farmacológica para a prevenção e limitação destas lesões. E, além disso, as formas disponíveis de intervenção não são totalmente eficazes. Recentemente, tem-se direcionado as atenções para os efeitos de produtos naturais na limitação dos danos provocados pela lesão de isquemia e reperfusão (I/R). Neste contexto, o timol, um monoterpeno fenólico, possui, dentre as suas atividades biológicas, ação antiinflamatória e antioxidante. Neste sentido, o objetivo do estudo foi avaliar o potencial efeito cardioprotetor do timol na prevenção da lesão de reperfusão pós-isquemia em ratos. Primeiramente foi realizado o ensaio de sequestros de radicais DPPH pelo timol. Para estudar seu potencial cardioprotetor, foram utilizados ratos Wistar machos (200-300 g) pré-tratados com timol (7,5 mg/kg, v.o.) ou veículo por 7 dias e submetidos a isquemia global do coração em sistema Langendorff. Foram avaliados parâmetros da função cardíaca como pressão desenvolvida pelo ventrículo esquerdo (PVDE), derivada temporal máxima (+Dp/dt) e mínima (-dp/dt) e índice de severidade da arritmia (ISA), tamanho da área de infarto, além de ensaios de atividade enzimática da catalase (CAT), Superóxido Dismutase (SOD), glutationas peroxidase (GPx) e redutase (GR), quantificação tecidual de sulfidrilas, bem como a concentração de substâncias reativas ao ácido tiobarbitúrico (TBARS) e hidroperóxidos de lipídeos. O ensaio de DPPH demonstrou propriedade antioxidante do timol. Além disso, foi observado que o pré-tratamento com timol preservou a PDVE, diminuiu o ISA, reduziu a área de infarto, TBARS e, de modo similar, foi observada menor concentração de hidroperóxidos quando comparado ao veículo. O pré-tratamento com timol preveniu a redução da concentração de grupamentos sulfidrila quando comparado ao veículo. As atividades das enzimas SOD, CAT, GPx e GR foram reduzidas de maneira significativa em corações de animais pré-tratados com timol quando comparados ao veículo. O pré-tratamento com timol preservou a função contrátil e cardíaca, reduziu danos aos componentes celulares e limitou a área de infarto. Demonstrando significativos efeitos cardioprotetores contra I/R.

The relationship between the PQ-segment slope on ST-segment depression during vigorous exercise was examined in 26 apparently healthy females between 18 and 26 years of age. Each subject performed 2 submaximal cycle ergometer exercise tolerance tests (trial A and trial B) on nonconsecutive days wherein the following variables, as delta scores, were measured; P-wave amplitude (microvolts), PQ-segment slope (uV!sec), and J-point at 0 and 60 msec (uV). Each variable was measured by both visual and computer averaging. The degree of reproducibility within and between trials differed for the visual and computer averaged measures. Generally higher reproducibility was found with computer averaging particularly within trial B (r =0.63-0.89, p<O.OI). Trial b served as a basis for assessment of PQ-segment slope effect on ST segment response. Computer analysis of frequency distribution for responses revealed a greater frequency of downsloping PQ-segment with clinically significant ST-segment depression (>50 uV) at both 0 and 60 msec after the J-point in lead II. However, there was a greater percentage (91%) of flat PQ-segment slopes with clinically significant ST-segment depression at J-point 0 msec in lead V5. These findings suggest possible influence of lead selection on the measurements of the PQ-segment slope and ST-segment. Implication of clinical application would be to use lead VS for diagnosing CHD and by measuring ST-segment depression at J-point 60 msec. However when screening exercise ECG tests in apparently healthy women use J-point at 0 msec. / Master of Science