TRPM4 inhibition by meclofenamate suppresses Ca2+-dependent triggered arrhythmias.

AIMS: Cardiac arrhythmias are a major factor in the occurrence of morbidity and sudden death in patients with cardiovascular disease. Disturbances of Ca2+ homeostasis in the heart contribute to the initiation and maintenance of cardiac arrhythmias. Extrasystolic increases in intracellular Ca2+ lead to delayed afterdepolarizations and triggered activity, which can result in heart rhythm abnormalities. It is being suggested that the Ca2+-activated nonselective cation channel TRPM4 is involved in the aetiology of triggered activity, but the exact contribution and in vivo significance are still unclear. METHODS AND RESULTS: In vitro electrophysiological and calcium imaging technique as well as in vivo intracardiac and telemetric electrocardiogram measurements in physiological and pathophysiological conditions were performed. In two distinct Ca2+-dependent proarrhythmic models, freely moving Trpm4-/- mice displayed a reduced burden of cardiac arrhythmias. Looking further into the specific contribution of TRPM4 to the cellular mechanism of arrhythmias, TRPM4 was found to contribute to a long-lasting Ca2+ overload-induced background current, thereby regulating cell excitability in Ca2+ overload conditions. To expand these results, a compound screening revealed meclofenamate as a potent antagonist of TRPM4. In line with the findings from Trpm4-/- mice, 10 µM meclofenamate inhibited the Ca2+ overload-induced background current in ventricular cardiomyocytes and 15 mg/kg meclofenamate suppressed catecholaminergic polymorphic ventricular tachycardia-associated arrhythmias in a TRPM4-dependent manner. CONCLUSION: The presented data establish that TRPM4 represents a novel target in the prevention and treatment of Ca2+-dependent triggered arrhythmias.

Implementation of a beating heart system for training in off-pump and minimally invasive coronary artery bypass.

BACKGROUND: Several training devices have been developed to train anastomotic skills in off-pump coronary artery bypass grafting (OPCAB). However, assessment of trainees' improvement remains challenging. The goal of this study was to develop a new practical scoring chart and investigate its reliability and utility for anastomotic skills in OPCAB and minimally invasive direct coronary artery bypass (MIDCAB). METHODS: A training device was used, which included a beating heart model installed in a dedicated box. A soft plastic tube was used as the left anterior descending artery, and a porcine ureter was used as the left internal mammary artery. Five cardiac surgery fellows (Fellows, > 5 year of surgical experience) and five residents or medical students (Residents, ≤ 5 year of surgical experience) were enrolled for this study. Before and after training, skills were evaluated using a scoring chart that took into account anastomotic time, leakage, shape, flow measurement, and self-estimation. RESULTS: Mean total score of all trainees was 15.4 ± 4.0 at pre-training and 18.5 ± 2.4 at post-training (P = 0.05). Before training, there was a significant difference in the total score between Fellows and Residents (18.6 ± 2.2 vs 12.2 ± 2.4 points, P = 0.002), which disappeared after training (19.4 ± 2.5 vs 17.6 ± 2.2 points, P = 0.262). Residents benefitted from training with improvements in their time, total score, score for time, score for flow and subtraction score; however, these effects were not seen in Fellows. The most evident training effect was improvement of self-estimation, which was also seen in Fellows. CONCLUSIONS: Residents were most likely to derive benefit from these training models with regard to both efficiency and quality. Training models seem to have an important role in making surgeons feel more comfortable with the procedure.

Packaging of implantable accelerometers to monitor epicardial and endocardial wall motion.

Acceleration signals, collected from the inner and the outer heart wall, offer a mean of assessing cardiac function during surgery. Accelerometric measurements can also provide detailed insights into myocardial motion during exploratory investigations. Two different implantable accelerometers to respectively record endocardial and epicardial vibrations, have been developed by packaging a commercially available capacitive transducer. The same coating materials have been deposited on the two devices to ensure biocompatibility of the implants: Parylene-C, medical epoxy and Polydimethylsiloxane (PDMS). The different position-specific requirements resulted in two very dissimilar sensor assemblies. The endocardial accelerometer, that measures accelerations from the inner surface of the heart during acute animal tests, is a 2 mm-radius hemisphere fixed on a polymethyl methacrylate (PMMA) rod to be inserted through the heart wall. The epicardial accelerometer, that monitors the motion of the outer surface of the heart, is a three-legged structure with a stretchable polytetrafluoroethylene (PTFE) reinforcement. This device can follow the continuous motion of the myocardium (the muscular tissue of the heart) during the cardiac cycle, without hindering its natural movement. Leakage currents lower than 1 µA have been measured during two weeks of continuous operation in saline. Both transducers have been used, during animal tests, to simultaneously record and compare acceleration signals from corresponding locations on the inner and the outer heart wall of a female sheep.

Robot-Assisted MIDCAB Using Bilateral Internal Thoracic Artery: A Propensity Score-Matched Study With OPCAB Patients.

OBJECTIVE: Robot-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB) is an attractive strategy for coronary revascularization. Growing evidence supports the use of total arterial grafting in coronary surgery. We evaluated total arterial left-sided coronary revascularization with bilateral internal thoracic artery (BITA) using RA-MIDCAB and compared it with a propensity score-matched (PSM) off-pump CAB (OPCAB) surgery population. METHODS: We retrospectively included all isolated OPCAB and RA-MIDCAB surgery using BITA without saphenous vein graft from January 1, 2015, to October 31, 2022. We analyzed all our RA-MIDCAB patients and performed PSM to compare them with our OPCAB population. Primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE) and mortality. Secondary outcomes were surgical parameters, length of hospital stay, and learning curve. RESULTS: We included 601 OPCAB and 77 RA-MIDCAB procedures, which resulted in 2 cohorts of 54 patients after PSM. Mortality and MACCE survival analysis showed no significant difference. There was less blood transfusion in the RA-MIDCAB (16.7%) compared with the OPCAB group (38.9%; P = 0.02). We observed fewer intensive care unit (ICU) admissions (24.1% vs 96.6%), shorter ICU stay (0.78 ± 1.7 vs 1.91 ± 1.01 days), and shorter hospital stay (6.78 ± 2.4 vs 8.01 ± 2.5 days) in the RA-MIDCAB versus OPCAB group (P < 0.01). Surgery time decreased from 400.0 ± 70.8 to 325.0 ± 38.0 min with more experience in RA-MIDCAB BITA harvesting (P < 0.01). CONCLUSIONS: This is a first publication of 77 consecutive RA-MIDCAB BITA harvesting for left coronary artery system revascularization. This technique is safe in terms of MACCE and mortality. Additional advantages are shorter length of hospital stay, fewer ICU admissions, and less blood transfusion.

Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds.

BACKGROUND: Reliable assessment of coronary microvascular function is essential. Techniques to measure absolute coronary blood flow are promising but need validation. The objectives of this study were: first, to validate the potential of saline infusion to generate maximum hyperemia in vivo. Second, to validate absolute coronary blood flow measured with continuous coronary thermodilution at high (40-50 mL/min) infusion speeds and asses its safety. METHODS: Fourteen closed-chest sheep underwent absolute coronary blood flow measurements with increasing saline infusion speeds at different dosages under general anesthesia. An additional 7 open-chest sheep underwent these measurements with epicardial Doppler flow probes. Coronary flows were compared with reactive hyperemia after 45 s of coronary occlusion. RESULTS: Twenty milliliters per minute of saline infusion induced a significantly lower hyperemic coronary flow (140 versus 191 mL/min; P=0.0165), lower coronary flow reserve (1.82 versus 3.21; P≤0.0001), and higher coronary resistance (655 versus 422 woods units; P=0.0053) than coronary occlusion. On the other hand, 30 mL/min of saline infusion resulted in hyperemic coronary flow (196 versus 192 mL/min; P=0.8292), coronary flow reserve (2.77 versus 3.21; P=0.1107), and coronary resistance (415 versus 422 woods units; P=0.9181) that were not different from coronary occlusion. Hyperemic coronary flow was 40.7% with 5 mL/min, 40.8% with 10 mL/min, 73.1% with 20 mL/min, 102.3% with 30 mL/min, 99.0% with 40 mL/min, and 98.0% with 50 mL/min of saline infusion when compared with postocclusive hyperemic flow. There was a significant bias toward flow overestimation (Bland-Altman: bias±SD, -73.09±30.52; 95% limits of agreement, -132.9 to -13.27) with 40 to 50 mL/min of saline. Occasionally, ischemic changes resulted in ventricular fibrillation (9.5% with 50 mL/min) at higher infusion rates. CONCLUSIONS: Continuous saline infusion of 30 mL/min but not 20 mL/min induced maximal hyperemia. Absolute coronary blood flow measured with saline infusion speeds of 40 to 50 mL/min was not accurate and not safe.

Remotely Triggered LAD Occlusion Using a Balloon Catheter in Spontaneously Breathing Mice.

Acute myocardial infarction (AMI) is a prevalent and high-mortality cardiovascular condition. Despite advancements in revascularization strategies for AMI, it frequently leads to myocardial ischemia-reperfusion injury (IRI), amplifying cardiac damage. Murine models serve as vital tools for investigating both acute injury and chronic myocardial remodeling in vivo. This study presents a unique closed-chest technique for remotely inducing myocardial IRI in mice, enabling the investigation of the very early phase of occlusion and reperfusion using in-vivo imaging such as MRI or PET. The protocol utilizes a remote occlusion method, allowing precise control over ischemia initiation after chest closure. It reduces surgical trauma, enables spontaneous breathing, and enhances experimental consistency. What sets this technique apart is its potential for simultaneous noninvasive imaging, including ultrasound and magnetic resonance imaging (MRI), during occlusion and reperfusion events. It offers a unique opportunity to analyze tissue responses in almost real-time, providing critical insights into processes during ischemia and reperfusion. Extensive systematic testing of this innovative approach was conducted, measuring cardiac necrosis markers for infarction, assessing the area at risk using contrast-enhanced MRI, and staining infarcts at the scar maturation stage. Through these investigations, emphasis was placed on the value of the proposed tool in advancing research approaches to myocardial ischemia-reperfusion injury and accelerating the development of targeted interventions. Preliminary findings demonstrating the feasibility of combining the proposed innovative experimental protocol with noninvasive imaging techniques are presented herein. These initial results highlight the benefit of utilizing the purpose-built animal cradle to remotely induce myocardial ischemia while simultaneously conducting MRI scans.

An interventional sheep model of severe aortic valve stenosis hemodynamics for the evaluation of alterations in coronary physiology and microvascular function.

We aimed to develop a large animal model of subcoronary aortic stenosis (AS) to study intracoronary and microcirculatory hemodynamics. A total of three surgical techniques inducing AS were evaluated in 12 sheep. Suturing the leaflets together around a dilator (n = 2) did not result in severe AS. Suturing of a pericardial patch with a variable opening just below the aortic valve (n = 5) created an AS which was poorly tolerated if the aortic valve area (AVA) was too small (0.38-1.02 cm2), but was feasible with an AVA of 1.2 cm2. However, standardization of aortic regurgitation (AR) with this technique is difficult. Therefore, we opted for implantation of an undersized AV-bioprosthesis with narrowing sutures on the leaflets (n = 5). Overall, five sheep survived the immediate postoperative period of which three had severe AS (one patch and two bioprostheses). The surviving sheep with severe AS developed left ventricular hypertrophy and signs of increased filling-pressures. Intracoronary assessment of physiological indices in these AS sheep pointed toward the development of functional microvascular dysfunction, with a significant increase in coronary resting flow and hyperemic coronary resistance, resulting in a significantly higher index of microvascular resistance (IMR) and lower myocardial resistance reserve (MRR). Microscopic analysis showed myocardial hypertrophy and signs of fibrosis without evidence of capillary rarefaction. In a large animal model of AS, microvascular changes are characterized by increased resting coronary flow and hyperemic coronary resistance resulting in increased IMR and decreased MRR. These physiological changes can influence the interpretation of regularly used coronary indices.NEW & NOTEWORTHY In an animal model of aortic valve stenosis (AS), coronary physiological changes are characterized by increased resting coronary flow and hyperemic coronary resistance. These changes can impact coronary indices frequently used to assess concomitant coronary artery disease (CAD). At this point, the best way to assess and treat CAD in AS remains unclear. Our data suggest that fractional flow reserve may underestimate CAD, and nonhyperemic pressure ratios may overestimate CAD severity before aortic valve replacement.

Angiotensin-converting enzyme inhibition and food restriction restore delayed preconditioning in diabetic mice.

BACKGROUND: Classical and delayed preconditioning are powerful endogenous protection mechanisms against ischemia-reperfusion damage. However, it is still uncertain whether delayed preconditioning can effectively salvage myocardium in patients with co-morbidities, such as diabetes and the metabolic syndrome. We investigated delayed preconditioning in mice models of type II diabetes and the metabolic syndrome and investigated interventions to optimize the preconditioning potential. METHODS: Hypoxic preconditioning was induced in C57Bl6-mice (WT), leptin deficient ob/ob (model for type II diabetes) and double knock-out (DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome). Twenty-four hours later, 30 min of regional ischemia was followed by 60 min reperfusion. Left ventricular contractility and infarct size were studied. The effect of 12 weeks food restriction or angiotensin-converting enzyme inhibition (ACE-I) on this was investigated. Differences between groups were analyzed for statistical significance by student's t-test or one-way ANOVA followed by a Fisher's LSD post hoc test. Factorial ANOVA was used to determine the interaction term between preconditioning and treatments, followed by a Fisher's LSD post hoc test. Two-way ANOVA was used to determine the relationship between infarct size and contractility (PRSW). A value of p<0.05 was considered significant. RESULTS: Left ventricular contractility is reduced in ob/ob compared with WT and even further reduced in DKO. ACE-I improved contractility in ob/ob and DKO mice. After ischemia/reperfusion without preconditioning, infarct size was larger in DKO and ob/ob versus WT. Hypoxic preconditioning induced a strong protection in WT and a partial protection in ob/ob mice. The preconditioning potential was lost in DKO. Twelve weeks of food restriction or ACE-I restored the preconditioning potential in DKO and improved it in ob/ob. CONCLUSION: Delayed preconditioning is restored by food restriction and ACE-I in case of type II diabetes and the metabolic syndrome.

Myocardial ischemia-reperfusion injury and the influence of inflammation.

Acute myocardial infarction is caused by a sudden coronary artery occlusion and leads to ischemia in the corresponding myocardial territory which generally results in myocardial necrosis. Without restoration of coronary perfusion, myocardial scar formation will cause adverse remodelling of the myocardium and heart failure. Successful introduction of percutaneous coronary intervention and surgical coronary artery bypass grafting made it possible to achieve early revascularisation/reperfusion, hence limiting the ischemic zone of myocardium. However, reperfusion by itself paradoxically triggers an exacerbated and accelerated injury in the myocardium, called ischemia-reperfusion (I/R) injury. This mechanism is partially driven by inflammation through multiple interacting pathways. In this review we summarize the current insights in mechanisms of I/R injury and the influence of altered inflammation. Multiple pharmacological and interventional therapeutic strategies (ischemic conditioning) have proven to be beneficial during I/R in preclinical models but were notoriously unsuccessful upon clinical translation. In this review we focus on common mechanisms of I/R injury, altered inflammation and potential therapeutic strategies. We hypothesize that a dual approach may be of value because I/R injury patients are predestined with multiple comorbidities and systemic low-grade inflammation, which requires targeted intervention before other strategies can be fully effective.

Erector spinae plane block for postoperative analgesia in robotically-assisted coronary artery bypass surgery: Results of a randomized placebo-controlled trial.

STUDY OBJECTIVE: To investigate if an erector spinae plane (ESP) block decreases postoperative opioid consumption, pain and postoperative nausea and vomiting in patients undergoing robotically-assisted minimally invasive direct coronary artery bypass surgery (RAMIDCAB). DESIGN: A single-center, double-blind, prospective, randomized, placebo-controlled trial. SETTING: Postoperative period; operating room, post-anesthesia care unit (PACU) and hospital ward in a university hospital. PATIENTS: Sixty-four patients undergoing RAMIDCAB surgery via left-sided mini-thoracotomy and enrolled in the institutional enhanced recovery after cardiac surgery program. INTERVENTIONS: At the end of surgery, patients received an ESP catheter at vertebra T5 under ultrasound guidance and were randomized to the administration of either ropivacaine 0.5% (loading dose of 30 ml and three additional doses of 20 ml each, interspersed with a 6 h interval) or normal saline 0.9% (with an identical administration scheme). In addition, patients received multimodal analgesia including acetaminophen, dexamethasone and patient-controlled analgesia with morphine. Following the final ESP bolus and before catheter removal, the position of the catheter was re-evaluated by ultrasound. Patients, investigators and medical personnel were blinded for the group allocation during the entire trial. MEASUREMENTS: Primary outcome was cumulative morphine consumption during the first 24 h after extubation. Secondary outcomes included location and severity of pain, presence/extent of sensory block, duration of postoperative ventilation and hospital length of stay. Safety outcomes comprised the incidence of adverse events. MAIN RESULTS: Median (IQR) 24-h morphine consumption was not different between the intervention- and control-groups, 67 mg (35-84) versus 71 mg (52-90) (p = 0.25), respectively. Likewise, no differences were detected in secondary and safety endpoints. CONCLUSIONS: Following RAMIDCAB surgery, adding an ESP block to a standard multimodal analgesia regimen did not reduce opioid consumption and pain scores.

Angiotensin-converting enzyme inhibition and food restriction in diabetic mice do not correct the increased sensitivity for ischemia-reperfusion injury.

BACKGROUND: The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On top of their diabetic cardiomyopathy, these patients experience frequent and severe cardiac ischemia-reperfusion (IR) insults, which further aggravate their degree of heart failure. Food restriction and angiotensin-converting enzyme inhibition (ACE-I) are standard therapies in these patients but the effects on cardiac IR injury have never been investigated. In this study, we tested the hypothesis that 1° food restriction and 2° ACE-I reduce infarct size and preserve cardiac contractility after IR injury in mouse models of diabetes and the metabolic syndrome. METHODS: C57Bl6/J wild type (WT) mice, leptin deficient ob/ob (model for type II diabetes) and double knock-out (LDLR-/-;ob/ob, further called DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome) were used. The effects of 12 weeks food restriction or ACE-I on infarct size and load-independent left ventricular contractility after 30 min regional cardiac ischemia were investigated. Differences between groups were analyzed for statistical significance by Student's t-test or factorial ANOVA followed by a Fisher's LSD post hoc test. RESULTS: Infarct size was larger in ob/ob and DKO versus WT. Twelve weeks of ACE-I improved pre-ischemic left ventricular contractility in ob/ob and DKO. Twelve weeks of food restriction, with a weight reduction of 35-40%, or ACE-I did not reduce the effect of IR. CONCLUSION: ACE-I and food restriction do not correct the increased sensitivity for cardiac IR-injury in mouse models of type II diabetes and the metabolic syndrome.

Robotic-assisted MIDCAB procedure through a minithoracotomy: Step-by-step instructions.

Minimally invasive cardiac surgery has evolved in recent years. Complex minimally invasive surgical techniques can further reduce the morbidity associated with surgical coronary bypass grafting. Robotic-assisted minimally invasive direct coronary artery bypass grafting is an effective and safe procedure in all risk groups. More experience with this procedure over the coming years should lead to the implementation of guidelines and the incorporation in heart-team decisions of schemes for individual patient care. We present a young male patient with familial hypercholesterolemia and chronic total occlusion of the left anterior descending artery (LAD) treated in January 2021 with a robotic-assisted minimally invasive direct coronary artery bypass graft through a minithoracotomy. The procedure was. The patient showed a fast recovery from the uncomplicated procedure and was discharged from the hospital after 3 days. We prepared this case report to facilitate training for this complex technical procedure. Robotic-assisted MIDCAB through a minithoracotomy is a technically demanding but safe minimally invasive alternative to coronary artery bypass grafting in patients with severe coronary lesions not suitable for percutaneous coronary intervention. In a hybrid coronary revascularization strategy, this technique minimizes surgical risk and optimizes long-term outcomes with high patency of surgical grafts.

Coronary revascularization in patients with HIV.

With combined antiretroviral therapy, people living with HIV (PLWH) survive longer and are now more likely to die from cardiovascular diseases. PLWH presenting with a ST-segment elevation myocardial infarction are likely to have a high thrombus burden and are at high risk for in-hospital and long-term adverse events. An increasing number of PLWH are presenting with stable coronary artery disease related to atherosclerosis. Revascularization in these patients is associated with higher in-hospital and long-term major adverse cardiovascular events, including stent thrombosis and in-stent restenosis. However, data in this expanding population concerning optimal revascularization strategy are still lacking. In particular, data comparing percutaneous versus surgical revascularization in PLWH are needed. In this review we highlight the currently available data related to coronary revascularization in PLWH.

Revascularization strategies in patients with multivessel coronary artery disease: a Bayesian network meta-analysis.

Treatment modalities for multivessel disease have rapidly evolved, yet the preferred strategy remains controversial. This meta-analysis compared outcomes after on-pump (ONCAB), off-pump coronary artery bypass grafting (OPCAB), percutaneous coronary intervention (PCI) or hybrid coronary revascularization. A comprehensive search for observational studies and randomized controlled trials published by August 2020 was performed. A Bayesian network meta-analysis was conducted for early (<30 days) and late (>12 months) outcomes. A total of 119 studies were included (n = 700 458 patients). The main analysis was confined to 31 randomized controlled trials (n = 24 932 patients). PCI was associated with lower early mortality [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.31-0.79] and stroke (OR 0.22, 95% CI 0.06-0.60) rates compared with ONCAB, whereas a reduced risk of early myocardial infarction was observed with OPCAB compared with ONCAB (OR 0.53, 95% CI 0.32-0.83). Late target vessel revascularization and major adverse cardiac and cerebrovascular events were both increased with PCI compared with ONCAB, OPCAB and hybrid coronary revascularization (by 127-203% and 59-64%, respectively), and late major adverse cardiac events were increased in PCI compared with ONCAB and OPCAB (by 64% and 59%). However, PCI was associated with a significantly lower risk of late stroke compared with ONCAB (OR 0.70, 95% CI 0.52-0.89). Sensitivity analyses (i) including observational studies and (ii) limiting to studies with recent cohorts confirmed the findings of the main analysis. Surgical approaches for revascularization remain superior to PCI in patients with multivessel disease. Hybrid coronary revascularization might be viable for some patients, although more evidence from randomized controlled trials is warranted.

Arteriovenous Fistulae in Chronic Kidney Disease and the Heart: Physiological, Histological, and Transcriptomic Characterization of a Novel Rat Model.

Background Arteriovenous fistulae (AVFs) are the gold standard for vascular access in those requiring hemodialysis but may put an extra hemodynamic stress on the cardiovascular system. The complex interactions between the heart, kidney, and AVFs remain incompletely understood. Methods and Results We characterized a novel rat model of five-sixths partial nephrectomy (NX) and AVFs. NX induced increases in urea, creatinine, and hippuric acid. The addition of an AVF (AVF+NX) further increased urea and a number of uremic toxins such as trimethylamine N-oxide and led to increases in cardiac index, left and right ventricular volumes, and right ventricular mass. Plasma levels of uremic toxins correlated well with ventricular morphology and function. Heart transcriptomes identified altered expression of 8 genes following NX and 894 genes following AVF+NX, whereas 290 and 1431 genes were altered in the kidney transcriptomes, respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed gene expression changes related to cell division and immune activation in both organs, suppression of ribosomes and transcriptional activity in the heart, and altered renin-angiotensin signaling as well as chronodisruption in the kidney. All except the latter were worsened in AVF+NX compared with NX. Conclusions Inflammation and organ dysfunction in chronic kidney disease are exacerbated following AVF creation. Furthermore, our study provides important information for the discovery of novel biomarkers and therapeutic targets in the management of cardiorenal syndrome.

Corrigendum: Robotic Cardiac Surgery in Europe: Status 2020.

[This corrects the article DOI: 10.3389/fcvm.2021.827515.].

Glucose tolerance and left ventricular pressure-volume relationships in frequently used mouse strains.

We investigated glucose tolerance and left ventricular contractile performance in 4 frequently used mouse strains (Swiss, C57BL/6J, DBA2, and BalbC) at 24 weeks. Glucose tolerance was tested by measuring blood glucose levels in time after intraperitoneal glucose injection (2 mg/g body weight). Left ventricular contractility was assessed by pressure-conductance analysis. Peak glucose levels and glucose area under the curve were higher (all P < .05) in C57BL/6J (418 ± 65 mg/dL and 813 ± 100 mg·h/dL) versus Swiss (237 ± 66 mg/dL and 470 ± 126 mg·h/dL), DBA2 (113 ± 20 mg/dL and 304 ± 49 mg·h/dL, P < .01), and BalbC mice (174 ± 55 mg/dL and 416 ± 70 mg·h/dL). Cardiac output was higher (all P < .05) in Swiss (14038 ± 4530 µL/min) versus C57BL/6J (10405 ± 2683 µL/min), DBA2 (10438 ± 3251 µL/min), and BalbC mice (8466 ± 3013 µL/min). Load-independent left ventricular contractility assessed as recruitable stroke work (PRSW) was comparable in all strains. In conclusion, glucose tolerance and load-dependent left ventricular performance parameters were different between 4 mice background strains, but PRSW was comparable.