scholarly journals Effects of ATP administration on isolated swine hearts: Implications for ex vivo perfusion and cardiac transplantation

2019 ◽  
Vol 244 (11) ◽  
pp. 915-922
Author(s):  
Maria S Seewald ◽  
Erik N Gaasedelen ◽  
Tinen L Iles ◽  
Lars M Mattison ◽  
Alexander R Mattson ◽  
...  

Cardiac transplant outcomes can be compromised by the effects of global ischemia and associated reperfusion injury. In attempts to alleviate these phenomena, various pharmaceutical agents can be administered. Previous reports have shown that adenosine triphosphate (ATP) may act as either a postconditioning (PoC) or supplementary (Sup) therapy with cardiosupportive benefits. To further evaluate ATP’s relative effectiveness, we used an isolated swine heart four-chamber working model to monitor both hemodynamic and metabolic responses. We employed two strategies of ATP administration: (1) a postconditional (PoC) bolus just prior to reanimation, and (2) regular dosing throughout the assessment period (Sup). Ex vivo swine hearts in the Sup group elicited significantly higher left ventricular function during the 2 h monitoring period than controls. In contrast, PoC administration appeared to induce depressed cardiac function. The effects of ATP on cardiac function can have varied effects, dependent on when it is administered. Impact statement We employed an isolated swine heart four-chamber working model to investigate two potential strategies for adenosine triphosphate (ATP) administration as an ex vivo therapy: (1) application of a single bolus dose during reperfusion (postconditioning or PoC), and (2) repeated bolus dosing throughout the experiment (supplementary or Sup). Ex vivo swine hearts in the Sup group elicited significantly higher left ventricular function during the 2 h experimental monitoring period. In contrast, ATP administration in the PoC group appeared to induce a degree of depressed hemodynamic function. These data suggest varied functional roles of ATP administration relative to their use in ex vivo perfusion strategies. We consider that both treatment strategies, if appropriately administered and with further investigation of dosing paradigms, may eventually elicit value in various clinical scenarios, including heart transplantation and ex vivo heart perfusion to assess potential organs for transplantation and potentially increase the pool of viable donor hearts.

2012 ◽  
Vol 303 (9) ◽  
pp. H1135-H1142 ◽  
Author(s):  
Sarah Mahne ◽  
Gin C. Chuang ◽  
Edward Pankey ◽  
Lucy Kiruri ◽  
Philip J. Kadowitz ◽  
...  

Epidemiological studies have consistently linked inhalation of particulate matter (PM) to increased cardiac morbidity and mortality, especially in at risk populations. However, few studies have examined the effect of PM on baseline cardiac function in otherwise healthy individuals. In addition, airborne PM contain environmentally persistent free radicals (EPFR) capable of redox cycling in biological systems. The purpose of this study was to determine whether nose-only inhalation of EPFRs (20 min/day for 7 days) could decrease baseline left ventricular function in healthy male Sprague-Dawley rats. The model EPFR tested was 1,2-dichlorobenzene chemisorbed to 0.2-μm-diameter silica/CuO particles at 230°C (DCB230). Inhalation of vehicle or silica particles served as controls. Twenty-four hours after the last exposure, rats were anesthetized (isoflurane) and ventilated (3 l/min), and left ventricular function was assessed using pressure-volume catheters. Compared with controls, inhalation of DCB230 significantly decreased baseline stroke volume, cardiac output, and stroke work. End-diastolic volume and end-diastolic pressure were also significantly reduced; however, ventricular contractility and relaxation were not changed. DCB230 also significantly increased pulmonary arterial pressure and produced hyperplasia in small pulmonary arteries. Plasma levels of C-reactive protein were significantly increased by exposure to DCB230, as were levels of heme oxygenase-1 and SOD2 in the left ventricle. Together, these data show that inhalation of EPFRs, but not silica particles, decreases baseline cardiac function in healthy rats by decreasing cardiac filling, secondary to increased pulmonary resistance. These EPFRs also produced systemic inflammation and increased oxidative stress markers in the left ventricle.


1996 ◽  
Vol 85 (5) ◽  
pp. 1063-1075 ◽  
Author(s):  
Stefan G. De Hert ◽  
Inez E. Rodrigus ◽  
Luc R. Haenen ◽  
Peter A. De Mulder ◽  
Thierry C. Gillebert

Background Impairment of left ventricular function after cardiopulmonary bypass (CPB) is well recognized, but little is known about the time course of recovery of cardiac function early after separation from CPB. Therefore, recovery of left ventricular function was evaluated early after separation from CPB in patients undergoing coronary artery surgery. The authors tried to determine whether this recovery might be attributed to autoregulation of function by preload. Methods Left ventricular pressure was measured with fluid-filled catheters. Data were digitally recorded during increased pressure induced by elevating the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/ml) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, ml-1) of the diastolic pressure-volume relation. Cardiac function was assessed before CPB, after termination of CPB, and 5, 10, and 15 min later. Two different separation procedures from CPB were compared: in protocol 1, left ventricular function was documented during the standard procedure (n = 24); in protocol 2, the heart was optimally filled 10 min before separation from CPB (n = 12). Results In protocol 1, Ees was 2.88 +/- 0.21 mmHg/ml (mean +/- SEM) and Kc was 0.012 +/- 0.001 ml-1 before CPB. Within 10 min after separation from CPB, Ees increased from 1.10 +/- 0.32 to 2.92 +/- 0.34 (P = 0.001) and Kc decreased from 0.022 +/- 0.002 to 0.011 +/- 0.001 (P = 0.001). The parameters remained stable thereafter. In protocol 2, Ees was 2.92 +/- 0.51 mmHg/ ml and Kc was 0.011 +/- 0.002 ml-1 before CPB. Depression of systolic and diastolic function was not observed in these patients. At time 0, Ees was 2.46 +/- 0.16 and Kc was 0.012 +/- 0.002. These values remained stable throughout the entire observation period. Conclusions Significant functional recovery was observed early after separation from CPB, which was suggestive of time-dependent changes in both systolic and diastolic left ventricular function induced by preload restoration.


2002 ◽  
Vol 49 (1) ◽  
pp. 27-35 ◽  
Author(s):  
M. Jovic ◽  
Zoran Popovic ◽  
Dusko Nezic ◽  
V. Ilic ◽  
Sinisa Gradinac ◽  
...  

Coronary artery bypass surgery in patient with bad left ventricular function is a challenge for surgical time. Specially important is monitoring of haemodynamics. We performed this open, prospective, randomized study with the aim to assess haemodynamics and oxygen profile monitoring. 34 pts for coronary surgery (EF < 40%) were divided in two groups. Group A, 17 pts. Received glucose-insulin-potassium (GIK) solution. Group B, 127 pts. Received Ringer solution. Haemodynamic and oxygen metabolism parameters were measured in four time points. I after the induction in anesthesia; II after the operation; III 6 hours post op.; IV 24 hour post op. Data are expressed as mean +/-SD, ANOVA for repeated measures followed by Newman-Keuls testing were used. In both groups were evident deterioration of cardiac function during first 6h as well as VO2 and DO:, more prominent in Group B. Significant recovery and improvement of cardiac function were evident in Group A after 24 h. CI during the time in Group A improves significantly (2.14+/-0.36 v. 3.05+/-0.55; p=0.0002) and difference during the time between groups was p=0,005. LVSWI improved significantly during the time him Group A (AIII vs. AIV) p=0.007. Simultaneously. VO improves significantly in Group A (103+/-21 vs. 164+/-30, p=0.00001) while difference between groups in DO was p=0.037. Importance of oxygen metabolism monitoring for both, left ventricular function and haemodynamics assessment was evident in our study.


2016 ◽  
Vol 39 (5) ◽  
pp. 2055-2064 ◽  
Author(s):  
Xue Cao ◽  
Zhijun Sun ◽  
Boya Zhang ◽  
Xueqi Li ◽  
Hongyuan Xia

Background/Aims: Plasma norepinephrine (NE) and brain natriuretic peptide (BNP, termed BNP-45 in rats) are considered as essential neurohormones indicating heart failure progression. The purposes of this study were to examine the effects of ivabradine (IBD) on cardiac function and plasma NE and BNP-45 after chronic ischemic heart failure (CHF) in non-diabetic rats and diabetic rats. We further determined if sympathetic NE uptake-1 (a major pathway to metabolize NE) mechanism is responsible for the role played by IBD. Methods: We ligated rat's coronary artery to induce CHF; and injected streptozotocin (STZ) to induce diabetic hyperglycemia. Echocardiography was employed to determine cardiac function. We used ELISA to examine plasma NE and BNP-45; and Western Blot analysis to examine the protein levels of NE uptake-1 in sympathetic nerves. Results: CHF increased the levels of NE and BNP-45 in non-STZ rats and STZ rats. Systemic injection of IBD significantly attenuated the augmented NE and BNP-45 and impaired left ventricular function induced by CHF in those rats. This effect appeared to be less in STZ rats. A liner relation was observed between the NE/BNP-45 levels and left ventricular function after administration of IBD. Also, IBD was observed to have a recovery effect on the downregulated NE uptake-1 evoked by CHF, but to a smaller degree in STZ rats. Conclusion: Our data revealed specific signaling mechanisms by which IBD improves the cardiac function as IBD alleviates impaired NE uptake-1and thereby decreases heightened NE and BNP-45 induced by CHF. Our data also demonstrated that the effects of IBD are weakened after diabetic hyperglycemia likely due to worsen NE uptake-1 pathway. Thus, targeting sympathetic NE uptake-1 signaling molecules has clinical implications for treatment and management of CHF in diabetes. Our data were also to shed light on strategies for application of this drug because NE and BNP play an important role in regulation of progression and prognosis of CHF, and in particular, because IBD affects NE uptake-1 pathway in hyperglycemic animals to a less degree.


2020 ◽  
Vol 319 (3) ◽  
pp. H642-H650
Author(s):  
B. Ruijsink ◽  
M. N. Velasco Forte ◽  
P. Duong ◽  
L. Asner ◽  
K. Pushparajah ◽  
...  

The right ventricle appears to have an important impact on maintaining systemic cardiac function and delivering stroke volume. However, its exact role in supporting left ventricular function has so far been unclear. This study demonstrates a new mechanism of ventricular interaction that provides mechanistic understanding of the key importance of the right ventricle in driving cardiac performance.


1986 ◽  
Vol 250 (6) ◽  
pp. H1117-H1126 ◽  
Author(s):  
P. A. Gwirtz ◽  
S. P. Overn ◽  
H. J. Mass ◽  
C. E. Jones

Modulation of coronary blood flow and cardiac function by alpha 1-adrenergic receptors was examined in dogs during strenuous exercise. Fifteen dogs were chronically instrumented to measure left circumflex blood flow, heart rate, regional left ventricular function (systolic shortening, and rate of shortening), and global left ventricular function (left ventricular pressure, and dP/dt). The specific postsynaptic alpha 1-receptor blocker prazosin (0.5 mg) and nonselective alpha-receptor blocker phentolamine (1.0 mg) were injected through an indwelling circumflex artery catheter to produce local adrenergic blockade of the posterior left ventricular region during exercise. Exercise significantly increased heart rate, left ventricular systolic pressure, dP/dt, segment shortening and rate of shortening, and coronary blood flow. Both prazosin and phentolamine caused similar additional increases in dP/dt by 21 +/- 4%, in rate of shortening in the posterior region by 37 +/- 6%, and in myocardial O2 consumption by 26 +/- 11%, which were associated with a 21 +/- 3% increase in coronary flow during exercise but no change in O2 extraction. Similar results were obtained when dogs were beta-blocked with either atenolol (1.0 mg ic) or propranolol (1.0 mg ic) prior to exercise. These data suggest that an alpha 1-vasoconstriction modulates O2 delivery to myocardial tissue and limits both coronary vasodilation and cardiac function during exercise.


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