The effect of a myocardial infarction on the normalized time-varying elastance curve

It has been suggested that the shape of the normalized time-varying elastance curve [E(n)(t(n))] is conserved in different cardiac pathologies. We hypothesize, however, that the E(n)(t(n)) differs quantitatively after myocardial infarction (MI). Sprague-Dawley rats (n = 9) were anesthetized, and the left anterior descending coronary artery was ligated to provoke the MI. A sham-operated control group (CTRL) (n = 10) was treated without the MI. Two months later, a conductance catheter was inserted into the left ventricle (LV). The LV pressure and volume were measured and the E(n)(t(n)) derived. Slopes of E(n)(t(n)) during the preejection period (alpha(PEP)), ejection period (alpha(EP)), and their ratio (beta = alpha(EP)/alpha(PEP)) were calculated, together with the characteristic decay time during isovolumic relaxation (tau) and the normalized elastance at end diastole (E(min)(n)). MI provoked significant LV chamber dilatation, thus a loss in cardiac output (-33%), ejection fraction (-40%), and stroke volume (-30%) (P < 0.05). Also, it caused significant calcium increase (17-fold), fibrosis (2-fold), and LV hypertrophy. End-systolic elastance dropped from 0.66 +/- 0.31 mmHg/microl (CTRL) to 0.34 +/- 0.11 mmHg/microl (MI) (P < 0.05). Normalized elastance was significantly reduced in the MI group during the preejection, ejection, and diastolic periods (P < 0.05). The slope of E(n)(t(n)) during the alpha(PEP) and beta were significantly altered after MI (P < 0.05). Furthermore, tau and end-diastolic E(min)(n) were both significantly augmented in the MI group. We conclude that the E(n)(t(n)) differs quantitatively in all phases of the heart cycle, between normal and hearts post-MI. This should be considered when utilizing the single-beat concept.

Effects of an aging vascular model on healthy and diseased hearts

Rafaela Fernandes Da Silva, David Jegger, Patrick Segers, Nikolaos Stergiopulos

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

2007

Coronary waves during valsalva maneuver measured during catheterization

Maria Cristina Rolandi

The mechanical interactions between heart contraction and perfusion of the heart are difficult to study in humans because of the restrictions in inducing changes in hemodynamic and cardiac mechanics parameters during catheterization. We hypothesize that the Valsalva maneuver can induce such alterations in the cardiac-coronary mechanical interaction and that these variations can be studied with the Wave Intensity Analysis. In order to interpret eventual changes in the wave intensity, a deep understanding of the effect of the Valsalva maneuver on the coronary circulation is needed. A particular attention has to be payed on the effect of the control of the microvascular resistance that is known to compensate for eventual alterations in the surrounding hemodynamic conditions when vessel tone is intact. In the catheterization laboratory, coronary pressure and flow velocity signals were recorded simultaneously by a new guidewire developed by Volcano Corporation. Aortic pressure, left ventricular pressure and ECG were acquired by the catheterization laboratory setup and recorded together with coronary hemodynamic signals. Left ventricular performance parameters were derived per beat from the noninvasive recording of the finger pressure using the Nexfin monitor developed by BMEYE B.V. In order to match the output data of coronary hemodynamic and left ventricular performance parameters, a dedicated program has been written in Delphi. An analysis of the per-beat data was performed in order to study the relative dependence of the parameters during the Valsalva maneuver. Pilot results of the Wave Intensity Analysis were obtained with an existing custom-made program also written in Delphi. Our study shows that the Valsalva maneuver caused a profound stress in the whole cardiovascular system. The well-known changes of the aortic pressure were transmitted also to the left ventricle and the coronary microcirculation. The data show that this stress caused a small but significant decrease in the flow velocity. As expected, the microvascular resistance varied with the same pattern as the coronary pressure trying to keep the flow constant. With respect to the decrease in stroke volume, cardiac output and contractility, the left ventricular performance was strongly compromised: pulse pressure generation and cardiac contraction were almost annulled. The decrease in systolic left ventricular pressure of almost 40% and the 2 fold increase in the end-diastolic left ventricular pressure confirm the decrease in the pumping action. Consequentially, the oxygen consumption of the heart decreased to 40% of the baseline level but only after an initial increase at the onset of the strain by 10%. The results also show that the timing of variation of the parameters was not the same. Especially the left ventricular end-diastolic pressure changed more rapidly than the perfusion pressure. Pilot results on Wave Intensity Analysis (WIA) show that the Valsalva maneuver gave rise to changes in the Wave Intensity pattern suggesting that the speed of the reflected waves has indeed been altered. Our results agree with previous studies that reveal a slight decrease in the flow velocity due to the Valsalva maneuver. Nevertheless, our results contradict the belief that ascribes the decrease in flow velocity to the decrease in oxygen consumption. We assume that the flow decrease is due to mechanical factors, especially the rise of left ventricular end-diastolic pressure. The results shown on WIA are pilot results and some work is still needed in this direction to obtain more information on the coronary-cardiac interaction. However, these results give confidence about the use of the Valsalva maneuver as an intervention affecting external parameters and thus they are useful in the study of coronary-cardiac interaction in humans.

2009

Effects of a stiffened arterial tree on ventricular-arterial coupling in healthy and diseased hearts

David Jegger

In this thesis we study ventricular-arterial coupling in rodents under the influence of arterial stiffening and myocardial infarction (MI), combination of the two considered as a novel cardiovascular research model for diseased hearts pumping against an aged, stiffened arterial tree. The stiffened arterial tree yields isolated systolic hypertension and is obtained by administration of vitamin D and nicotine (VDN). The investigation cardiac performance and ventricular-arterial coupling using such a combined model (VDN/MI) is of particular relevance to cardiac research, as cardiac disease in elderly often takes place in presence of a atherosclerotic or stiff arterial tree.. The thesis consists of an Introduction, 4 scientific papers and a brief Conclusion. The Introduction is an overview of the epidemiology of heart failure, structure and functional changes that occur during MI and VDN, material and methods used in evaluating cardiac function invasively and non-invasively (using trans-thoracic echocardiography, TTE), methods for evaluating arterial function, and finally an overview of the interaction between the heart and vessels. Paper 1: This paper addresses the issue of the universality of the normalized time-varying elastance curve. It is demonstrated that the waveform of the normalized time-varying elastance curve (En(tn)) is qualitatively comparable between the control and MI hearts, however, when En(tn) is compared quantitatively between the two groups, statistical significance is found at the ejection phase and during diastole. These differences need to be taken into account when assessing cardiac contractility based on a generalized En(tn) in different animal models or in the human in different physiological or pathological states. Paper 2: Using trans-thoracic echo (TTE), we were able to follow serial changes of cardiac function post MI using two novel parameters, the myocardioal performance index (MPI) and its ratio to left ventricular fractional shortening (LVFS/MPI), both indices being monitor successfully and as efficiently as other classical TTE parameters. More so, LVFS/MPI visually expressed better the serial modifications in cardiac function. Both MPI and LVFS/MPI were correlated to the load-independent contractile parameter, PRSW, and to the preload parameter, LVEDP, being thus pertinent in following preload changes post MI. Finally, chamber remodeling post MI can successfully be followed due to the fact that ESV and EDV both correlate to MPI and LVFS/MPI. Paper 3: We studied hemodynamics, arterial function, cardiac function and ventricular-arterial coupling in a rat model of reduced arterial compliance. The results show that arterial stiffening after VDN treatment provokes important changes in vascular impedance and wave reflections, leading to isolated systolic hypertension and LV hypertrophy, Ventricular-arterial coupling was also altered. The effects are quantitatively similar to those of arterial stiffening with age. Paper 4: We studied changes in cardiac geometry, structure and function in response to MI in control and VDN-treated (stiffened aorta) rats. The combined VDN/MI model showed the largest compromise in cardiac structure and function and exhibited the strongest biochemical signs of heart failure as compared to all other groups. The addition of MI on top of a raised afterload, seems to have accelerated the progression of heart failure. Vascular alterations also reflected well a model of ageing and calcification. This combined pathology model of failing hearts in presence of a stiff arterial tree might be fruitful in better understanding the evolution of disease and may help improving or developing novel treatment therapies. The Conclusion chapter summarizes the findings of the thesis and brings into perspective their importance and future relevance into cardiovascular research models.