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The ability of the adult heart to generate new myocytes after injury is not established. Our purpose was to determine if the adult heart has the capacity to generate new myocytes after injury, and to gain insight into their source. Cardiac injury was induced in the adult feline heart by infusing Isoproterenol (ISO) for 10 days with minipumps and then animals were allowed to recover for 7 or 28 days. Cardiac function was measured with echocardiography and proliferative cells were identified by nuclear incorporation of 5-bromodeoxyuridine (BrdU; 7 day minipump infusion). BrdU was infused for 7 days before euthanasia at Day 10 (injury), Day 17 (early recovery), and Day 38 (late recovery) and, with a separate group of animals, was infused during injury and removed at Day 10, with animals euthanized at Day 38 for a pulse-chase experiment. Isoproterenol caused a reduction in cardiac function with evidence of myocyte loss from necrosis. During the injury phase there was a significant increase in the number of proliferative cells in the atria and ventricle, including an increase in cKit+/BrdU+ proliferative cardiac precursor cells, but there was no increase in the number of BrdU+ new myocytes (Day 10). During the first seven days of recovery (Day 17) there was a significant reduction in cellular proliferation (total BrdU+ nuclei, including cKit+/BrdU+ proliferative cardiac precursor cells) but a significant increase in BrdU+ myocytes. There was modest improvement in cardiac structure and function during recovery. At Day 38 (late recovery), overall cell proliferation (BrdU+ cells) was not different than control (BrdU infused from Days 31-38); however, increased numbers of ("bright") BrdU+ myocytes were found at Day 38 in the pulse-chase experiment, when BrdU was infused during injury (and removed at Day 10). Some of the newly formed myocytes (from the pulse-chase group; Day 38), derived from BrdU+ cardiac precursors appear to be transiently proliferative (between Days 10-38) producing a population of "dimly" BrdU+ myocytes in our pulse-chase protocol (BrdU infused during injury, Days 3-10, and removed at Day 10, with heart explant at Day 38). No significant numbers of "dimly" BrdU+ nuclei were found in any of the hearts in which BrdU was infused for 7 days prior to the animal being euthanized (Control, Day 10, Day 17, Day 38). These observations are most consistent with the conclusions stated. Our results also suggest that myocyte regeneration, as defined by BrdU+ myocytes, was more robust in the atria than the ventricle. The reasons for these differences are not clear and deserve additional study. If true, our findings suggest that cardiac precursors isolated and expanded from atrial tissue might be a better source of cells for autologous cardiac cell therapy. In summary, our data shows that the adult heart has the ability to generate new myocytes after injury, suggests that ISO injury activates cardiac precursor cells that can differentiate into new myocytes during cardiac repair, but that the environment of the ISO injured heart blunts the differentiation of cardiac precursors into functional new myocytes. The contribution of new myocytes to improved function of the ventricle would appear to be small, unless we have underestimated the number of these cells. This is quite possible, and further study is warranted to incorporate the number of "dimly" BrdU+ myocytes that may have undergone a proliferative phase as a progenitor cell and/or as an immature cardiac myocyte. Further understanding the factors that limit endogenous new myocyte formation could significantly contribute to new therapeutic applications and improve the quality of life, and potentially the lifespan, of patients in heart failure. / Physiology

The study of cardiac regeneration can have many forms in which it is defined. It can not only be the ability to add new myocardium to dead or dying tissues, but also include the prevention of cardiac tissue degeneration, reversal of tissue remodeling, and the maintenance of systolic and diastolic function in the incidence of tissue damage, which can lead to subsequent heart failure progression. The use of stem cells for cardiac regeneration represents a growing field of new therapies for patients with end stage cardiac disease. Various studies have noted promising results in the recovery and reparation of these tissues. Cumulatively, their goals have become the identification of the most suitable cell type, as well as how to maximize functional efficiency and cost effectiveness for practical application. Many protocols simply do not ensure adequate cell engraftment, viability, and ultimately the return of normal tissue function. Investigators seek to determine how these processes can be enhanced or manipulated to promote cardiac regeneration in hopes of eventually making their clinical use a standard practice. / Physiology

The mortality/morbidity and quality of life benefits of exercise-based cardiac rehabilitation (CR) are well established, yet adherence to exercise is generally poor post-discharge. Recent trials have attempted to enhance adherence to aerobic activities during transition from CR to home-based exercise. However, these trials have not addressed resistance training, which is also an integral part of many participants' CR exercise routines. Because accessibility to familiar training equipment (e.g., weight machines) and instruction may be limited for many patients upon completion of CR, poor adherence to this beneficial form of exercise can be resultant. The purpose of this study was to examine the effects of a brief intervention involving the provision of a motivation-enhancing instructional manual and elastic Thera-Bands® on self-efficacy for, outcome expectancies for, and adherence to, upper body resistance exercise. It was hypothesized that participants receiving the intervention would report higher self-efficacy, outcome expectancies and greater adherence than those in a standard care control condition. The study was a randomized controlled trial involving informed and consenting CR participants recruited from an established outpatient CR programme at a major urban hospital (N = 40; n_males = 32; M_age= 61.20 ± 11.10). Participants in the intervention group (n=20) received an orientation to home-based upper body resistance training, a theory-based instructional manual designed to enhance self-efficacy and outcome expectations, and Thera-Bands®. The standard care control group received an orientation to home-based upper body resistance training and standard care CR follow-up (n=20). Participants completed baseline measures of self-efficacy for performing resistance training and activities of daily living as well as outcome expectancy measures one week prior to discharge from CR. The same measures were completed again one week later (i.e., at the end of the CR program), and at 4-weeks post-discharge. Participants logged their sets of upper-body resistance exercises continuously throughout the 4-week period following completion of the CR program. There were no differences between groups on any of the study variables at baseline. Participants in the intervention condition reported higher self-efficacy and outcome expectations for resistance training than controls at the 4-week follow-up assessment. Adherence to resistance training was significantly greater with the intervention group completing over twice as many (105%) sets over the four weeks than the control group. Maintaining or increasing upper body strength is an important outcome of CR as it relates to the performance of many activities of daily living. However, adherence to resistance exercises may be difficult upon completion of supervised, facility-based CR. This study illustrates that the provision of a motivation-enhancing instructional manual and low cost materials has a positive impact on self-efficacy, outcome expectations and adherence to resistance training, and may help participants make a successful transition to home-based resistance exercise. / Thesis / Master of Science (MS)

The purpose of this thesis investigation was to evaluate the effects of combined aerobic and weightlifting training on the circulatory responses of patients with coronary artery disease (CAD) during formal lifting, and during strength related activities of daily living. Seven subjects (x age: 54 years) successfully completed 20 sessions of training within 12 weeks. The aerobic training regimen consisted of a 5-10 minute warm up, walking, arm buoys, and arm-and leg-cycling at an intensity equivalent to approximately 70% of functional capacity. The weightlifting regimen consisted of single-arm curl (SAC), and single-leg press (SLP) exercises performed by both limbs, in addition to modified trunk curls. Before and after training, intra-brachial artery pressure was measured continuously during: 10 repetitions of the seated SAC exercise at 70% of the subject's one repetition maximum (1 RM), 12 repetitions of the SLP and double-leg press (DLP) exercises at 80% of 1 RM, isometric handgrip at 50% of maximal voluntary contraction strength, 10 flights of stair climbing at a cadence of 60 steps/minute, and 10 minutes of horizontal treadmill walking at 3.5 mph. Training increased the SAC, SLP, and DLP 1 RM strength by 98% (15 vs 30 kg; p < 0.016), 23% (99 vs 122 kg; p < 0.002), and 27% (165 vs 210 kg; p < 0.001) respectively. The mean peak systolic, diastolic, and mean arterial pressures, heart rate and rate pressure product were attenuated in all 3 weightlifting exercises when subjects lifted the same absolute load (70% of the pre-training 1 RM for the SAC exercise, and 80% of the pre-training 1 RM for the SLP and DLP exercises) after training. When subjects lifted the same relative load after training, all circulatory responses increased. The average peak heart rate and arterial pressure responses were reduced during 10 minutes of horizontal treadmill walking after training. In contrast, there was little or no reduction in any of the measured parameters during stair climbing. It is concluded that weightlifting training in CAD patients results in an attenuation of the heart rate and arterial blood pressure responses during repeated lifting with identical absolute loads, and there may be a modest transfer of this effect to certain activities of daily living involving the trained muscles. / Thesis / Master of Science (MS)

Cardiovascular diseases (CVD) are the leading cause of death around the world, being responsible for 31.8% of all deaths in 2017. The leading cause of CVD is Ischemic heart disease (IHD), which caused 8.1 million deaths in 2013. IHD occurs when coronary arteries in the heart are narrowed or blocked, preventing the flow of oxygen and blood into the cardiac muscle, which could provoke acute myocardial infarction (AMI) and ultimately lead to heart failure and death. Cardiac regenerative therapy aims to repair and refunctionalize damaged heart tissue through the application of (1) intramyocardial cell delivery, (2) epicardial cardiac patch, and (3) acellular biomaterials. These approaches have provided benefit of cell localization and tissue structure respectively. However, to improve cell retention and integration, there is a need for the intramyocardial delivery of functional tissues while preserving anisotropic muscle alignment. Here, we developed a biodegradable z-wire scaffold that supports the scalable gel-free production of an array of functional cardiac tissues in a 384-well plate format. The z-wire scaffold design supports cellular alignment, provides tunable mechanical support, and allows for hallmark tissue contraction. When the scaffold is imparted with magnetic properties, individual tissues can be assembled with macroscopic alignment under magnetic guidance. When used in combination with a customized surgical delivery tool, z-wire tissues can be injected directly into the myocardial wall, with controlled tissue orientation according to the injection path. This modular tissue engineering approach, in combination with the use of smart scaffolds, could expand opportunity in functional tissue delivery. / Thesis / Master of Science in Chemical Engineering (MSChE)

Advances in technology have now made it possible to analyze cardiac output (Q) with only a single-breath, making measurements during exercise quicker and less invasive for the subject. Certain non-invasive techniques allow for measurement of the disappearance of a soluble inert gas as it diffuses across the blood-gas barrier in the lungs. The rate of disappearance of the gas is directly proportional to the flow of blood past the lungs and subsequently provides an estimate of pulmonary capillary blood flow (Qc), or Q. The SensorMedics® Corporation (Yorba Linda, CA) has developed a single-breath acetylene (C₂H₂) technique (SensorMedics Vmax 229TM), which includes a simple device to linearize expiratory flow rate by increasing the time by which the sensors can measure the disappearance of the marker gas and improve quantification. The purpose of this investigation was to determine the reproducibility of the C₂H₂ single-breath technique during ramping exercise testing with the addition of a starling resistor in 11 apparently healthy, sedentary volunteers (7 male and 4 female). Subjects performed three maximal ramping exercise test sessions over a 6-week period and Qc was measured at rest and at three time points during the exercise test. The C₂H₂ single-breath Qc measurement technique was shown to be repeatable when systematically related to VO₂ (Qc/VO₂ relation highly correlated r² = 0.72-.74), but slightly lower than previously reported. Means and 95% confidence intervals revealed the precision of the technique over repeated testing days. This method was able to capture Qc measurements at intensities greater than 75% VO₂pk in all subjects with the use of the Starling resistor. Bland-Altman plots reveal Qc measures to be about 50% more variable than highly reproducible measures such as VO₂ and HR. Intraclass reliability coefficients (r) found through repeated measures ANOVA were found to perform low (rx,x= -0.11-0.31) from rest throughout all intensities of exercise. This device is limited in the ability of the sensors to accurately analyze Qc with subjects who are unfamiliar and have difficulty with the single-breath maneuver. Such instances make it difficult for objective, accurate determinations to be made by the clinician. The C₂H₂ single-breath method was found to capture Qc at higher intensities and a high level of precision with the addition of the starling resistor. However, more evidence needs to be analyzed before use of this device can be put into clinical practice. / Master of Science

From the introduction: What follows in the next pages is a tabulation of results of open heart surgery in 1880 patients who were admitted to the cardiovascular surgery unit during the period May, 1956-May, 1969. Surgical mortality and morbidity data are presented in a brief manner. I have tried to interpret the results in light of the similar experience of others. This digestion of the work of others with enzymes of one's personal experience is not always palatable, especially when the latter is admittedly limited.