Comparative evaluation of empagliflozin, canagliflozin and sitagliptin cardioprotective properties in rats with experimental type 2 diabetes mellitus

Background: Myocardial infarction (MI) is one of the leading causes of mortality in patients with type 2 diabetes mellitus (DM), therefore it is essential to give preference to a glucose-lowering drug having optimal cardioprotective properties. A comparative study of the various sodium-glucose co-transporter inhibitors representatives’ protective effects in experimental MI was not carried out within the framework of one study.Aim: To evaluate the influence of empagliflozin (EMPA) and canagliflozin (CANA), in comparison with sitagliptin (SITA), on hemodynamic parameters and myocardial damage area in rats with diabetes type 2 model in experimental MI.Materials and methods: Type 2 DM was modelled in Wistar rats by means of 4-week high-fat diet followed by nicotinamide 230 mg/kg and streptozotocin 60 mg/kg administration. 4 weeks after DM induction the following groups were made: «DM+SITA» — treatment with SITA 50 mg/kg, «DM+EMPA» — treatment with EMPA 2 mg/kg, «DM+CANA» — treatment with CANA 25 mg/kg per os once daily for 8 weeks. Animals in «DM» group remained untreated for the following 8 weeks. Rats in control group were fed with standard chow. 16 weeks after the experiment beginning transient global myocardial ischemia was modelled in all rats. Hemodynamic parameters and myocardium necrosis area were evaluated.Results: The necrosis area was larger in «DM» group, than in control one (p=0.018). Infarction size in «DM+SITA» did not differ from that in «DM» group (62.92(41.29;75.84) and 57.26(45.51;70.08)%, р=0.554). Necrosis area in «DM+EMPA» and «DM+CANA» groups was smaller than in «DM» group (37.90(20.76;54.66)%, 46.15(29.77;50.55) vs 57.26(45.51;70.08)%, р=0.008 and р=0.009, respectively). Necrosis size did not differ between «DM+EMPA» and «DM+CANA» groups (p=0.630). Ischemic contracture in «DM+CANA» group was less prominent than under the use of all other glucose-lowering drugs. We observed increase of coronary blood flow in «DM+EMPA» group, in comparison with «DM», «DM+CANA» and «DM+SITA» groups.Conclusions: SITA does not have cardioprotective effect in ischemia-reperfusion injury in diabetic rats. EMPA and CANA have similarly prominent infarct-limiting properties. EMPA is able to increase coronary blood flow, whereas cardioprotective action of CANA is associated with ischemic contracture diminishing.

Ischemic Contracture following Compartment Syndrome Diagnosed 16 Months after Total Knee Arthroplasty: A Case Report and Review of the Literature

Compartment syndrome is a rare complication of total knee arthroplasty (TKA) that if left untreated can result in irreversible neurologic deficits and muscle damage, ultimately causing loss of lower limb function, organ failure, and rarely death. Compartment syndrome following TKA may be misdiagnosed as vascular injury, peroneal nerve palsy, deep vein thrombosis, or postoperative pain and swelling, which may delay treatment. Here, we present the case of a 56-year-old female presenting with signs of common peroneal nerve neuropathy 16 months after undergoing ipsilateral TKA. Exploration of the common peroneal nerve demonstrated chronic ischemic changes with muscle necrosis within the lateral and anterior leg compartments. This case highlights compartment syndrome as a rare complication following TKA and presents the sequelae and treatment of ischemic contracture.

Management of Volkmann’s Ischemic Contracture: Case Series of 32 patients

Introduction: Volkmann’s contracture condition is of high prevalence in our population and is linked to therapeutic faults. The treatment and its results are determined according to the severity of the lesions. Methods: This retrospective study was performed in three centers and was conducted over 30 years (1987–2018); it included 32 patients. The disabilities of the arm, shoulder and hand (DASH) score and the Weber test were used to evaluate the functional outcome looking at mid and long-term results. Results: Thirty-two patients were treated for Volkmann’s Ischemic Contracture (VIC). The age ranged from 4 to 58 years, with 19 patients aged under 15. Wrist fracture was the predominant cause in 16 cases. Fourteen patients obtained a completely functional hand, seven good functional results, four fair functional results, and seven poor results. Discussion: In comparison with other studies, we noticed significant differences: apart from the dominant male sex and right side, this is one large case series conducted over 30 years (1987–2018) looking at mid-and long-term results. All the patients presented with severe or moderate lesions on the first visit. In our study, the wrist fracture is predominant compared to elbow fractures and soft trauma. X-rays are especially helpful and are a first-line investigation for identifying displaced fractures and other associated lesions. Our study population is not large, and the treatment methods are varied, so it is impossible to provide statistically relevant correlations between the treatment method and outcome. But this work is based on the experience of more than 30 years, which makes it possible to help adequate decision making according to the state of the lesions. This study is a level IV case series.

Elevated perfusate [Na+] increases contractile dysfunction during ischemia and reperfusion

Recent studies revealed that relatively small changes in perfusate sodium ([Na+]o) composition significantly affect cardiac electrical conduction and stability in contraction arrested ex vivo Langendorff heart preparations before and during simulated ischemia. Additionally, [Na+]o modulates cardiomyocyte contractility via a sodium-calcium exchanger (NCX) mediated pathway. It remains unknown, however, whether modest changes to [Na+]o that promote electrophysiologic stability similarly improve mechanical function during baseline and ischemia–reperfusion conditions. The purpose of this study was to quantify cardiac mechanical function during ischemia–reperfusion with perfusates containing 145 or 155 mM Na+ in Langendorff perfused isolated rat heart preparations. Relative to 145 mM Na+, perfusion with 155 mM [Na+]o decreased the amplitude of left-ventricular developed pressure (LVDP) at baseline and accelerated the onset of ischemic contracture. Inhibiting NCX with SEA0400 abolished LVDP depression caused by increasing [Na+]o at baseline and reduced the time to peak ischemic contracture. Ischemia–reperfusion decreased LVDP in all hearts with return of intrinsic activity, and reperfusion with 155 mM [Na+]o further depressed mechanical function. In summary, elevating [Na+]o by as little as 10 mM can significantly modulate mechanical function under baseline conditions, as well as during ischemia and reperfusion. Importantly, clinical use of Normal Saline, which contains 155 mM [Na+]o, with cardiac ischemia may require further investigation.